Drug delivery device, method of manufacture, and method of use

ABSTRACT

Disclosed herein is a wearable drug delivery device including a container filled at least partially with a drug including at least one of a PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) specific antibody, a granulocyte colony-stimulating factor CSF), a sclerostin antibody, or a calcitonin gene-related peptide (CGRP) antibody. The wearable drug delivery device includes a needle and an insertion mechanism configured to insert the needle into a patient. A fluid pathway connector defines a sterile fluid flowpath between the container and the insertion mechanism. A cannula initially disposed about the needle is included.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of each of U.S. ProvisionalPatent Application No. 62/320,438, filed Apr. 8, 2016, and InternationalPatent Application No. PCT/US2017/017627, filed Feb. 13, 2017. Theentire contents of each of the foregoing are expressly incorporated byreference herein for all purposes.

FIELD OF THE DISCLOSURE

The present disclosure generally relates to drug delivery devices and,more particularly, a drug delivery device capable of being worn by apatient while the drug delivery device delivers a drug to the patient.

BACKGROUND

Parenteral delivery of various drugs, i.e., delivery by means other thanthrough the digestive track, has become a desired method of drugdelivery for a number of reasons. This form of drug delivery byinjection may enhance the effect of the substance being delivered andensure that the unaltered medicine reaches its intended site at asignificant concentration. Similarly, undesired side effects associatedwith other routes of delivery, such as systemic toxicity, canpotentially be avoided through parenteral delivery. By bypassing thedigestive system of a mammalian patient, one can avoid degradation ofthe active ingredients caused by the catalytic enzymes in the digestivetract and liver and ensure that a necessary amount of drug, at a desiredconcentration, reaches the targeted site.

Traditionally, manually operated syringes and injection pens have beenemployed for delivering parenteral drugs to a patient. More recently,parenteral delivery of liquid medicines into the body has beenaccomplished by administering bolus injections using a needle andreservoir, continuously by gravity driven dispensers, or via transdermalpatch technologies. Bolus injections often imperfectly match theclinical needs of the patient, and usually require larger individualdoses than are desired at the specific time they are given. Continuousdelivery of medicine through gravity-feed systems compromises thepatient's mobility and lifestyle, and limits the therapy to simplisticflow rates and profiles. Another form of drug delivery, transdermalpatches, similarly has its restrictions. Transdermal patches oftenrequire specific molecular drug structures for efficacy, and the controlof the drug administration through a transdermal patch is severelylimited.

Ambulatory infusion pumps have been developed for delivering liquidmedicaments to a patient. These infusion devices have the ability tooffer sophisticated fluid delivery profiles accomplishing bolusrequirements, continuous infusion and variable flow rate delivery. Theseinfusion capabilities usually result in better efficacy of the drug andtherapy and less toxicity to the patient's system. Currently availableambulatory infusion devices are expensive, difficult to program andprepare for infusion, and tend to be bulky, heavy and very fragile.Filling these devices can be difficult and require the patient to carryboth the intended medication as well as filling accessories. The devicesoften require specialized care, maintenance, and cleaning to assureproper functionality and safety for their intended long-term use, andare not cost-effective for patients or healthcare providers.

As compared to syringes and injection pens, pump type delivery devicescan be significantly more convenient to a patient, in that doses of thedrug may be calculated and delivered automatically to a patient at anytime during the day or night. Furthermore, when used in conjunction withmetabolic sensors or monitors, pumps may be automatically controlled toprovide appropriate doses of a fluidic medium at appropriate times ofneed, based on sensed or monitored metabolic levels. As a result, pumptype delivery devices have become an important aspect of modern medicaltreatments of various types of medical conditions, such as diabetes, andthe like.

While pump type delivery systems have been utilized to solve a number ofpatient needs, manually operated syringes and injection pens oftenremain a preferred choice for drug delivery as they now provideintegrated safety features and can easily be read to identify the statusof drug delivery and the end of dose dispensing. However, manuallyoperated syringes and injections pens are not universally applicable andare not preferred for delivery of all drugs. There remains a need for anadjustable (and/or programmable) infusion system that is precise andreliable and can offer clinicians and patients a small, low cost, lightweight, simple to use alternative for parenteral delivery of liquidmedicines.

There is a strong market demand for drug delivery devices which areeasy-to-use, cost-efficient, and which include integrated safetyfeatures. However, manufacturing of such devices can be cost intensive,which results in higher costs to patients. Much of the manufacturingcosts can be attributed to the need to maintain a sterile fluid pathwayfrom the drug container to the needle, prior to introduction of the drugto the patient. Some commercial products seek to maintain the sterilityof the device by manufacturing the components in a non-sterileenvironment and then sterilizing the entire device. A recognizeddownside of such processes is the need to separately fill the drugcontainer after device sterilization but prior to drug injection, asmost pharmaceutical compounds are not capable of withstanding the devicesterilization process. Alternatively, the drug delivery device may bemanufactured as a pre-filled device, wherein the device is filled withthe drug aseptically during assembly. Such manufacturing processes maybe costly since the entire process must be kept sterile and because thefill and assembly lines need to be specially-tailored for the device.Accordingly, this adds substantial operating costs to pharmaceuticalcompanies and contract drug-fillers.

Drug delivery devices are generally prepared by molding or shaping thevarious components and then assembling the components. The assemblingsteps and other processing operations typically produce a device thatsubsequently must be cleaned to remove particulates adhering to thesurfaces to satisfy cleanliness standards for drug delivery devices.After cleaning, conventional drug delivery devices are packaged andsterilized. Such delivery devices have been classified into severalgeneral types. The first type is assembled and placed in sterilepackaging which can be shipped with a vial or ampoule of a drug or otherinjectable solution. The delivery device is filled with the drug orother solution at the point of use and injected into the patient. Thesedevices have the disadvantage of increasing the time and difficulty offilling the device at the point of use, increasing the risk ofcontamination of the delivery device and/or drug solution, andincreasing the likelihood of accidental spills of the drug. There is afurther risk of glass particles from the ampoules contaminating the drugsolution when the ampoules are opened. Furthermore, the healthcareprovider and/or patient may be require training to ensure that they fillthe device properly

Several of these disadvantages are overcome by providing prefilleddelivery devices which can be filled with a suitable drug solution priorto use. Prefilled delivery devices, as the term is known in the art, aredevices that are filled by the drug manufacturer and shipped to thehealth care provider or self-administering patient in a condition thatis ready for use. The vial or ampoule is generally made of glass orother clear material that does not interfere with the stability of thedrug during prolonged storage. Prefilled delivery devices have theadvantage of convenience and ease of application with reduced risk ofcontamination of the drug solution. Prefilled drug delivery devices aregenerally assembled and packaged in clean rooms to maintain propercleanliness levels. The clean rooms are equipped with extensive filterassemblies and air control systems to remove particulates and pyrogensfrom the air in the room and to prevent particulates and pyrogens fromentering the room. The operators and other personnel in the clean roomare required to wear appropriate protective garments to reducecontamination of the air and the drug delivery devices beingmanufactured or assembled. As people and equipment enter and leave theclean room, the risk of contamination and introduction of foreignparticulates and pyrogens increases. Various operations are able to formclean and sterile drug delivery devices. However, subsequent handling,filling and printing of the drug delivery device can contaminate thedevice. It is then necessary to clean and sterilize such conventionaldrug delivery devices before use. Accordingly, there is a continuingneed in the industry for an improved system for manufacturing andassembling clean and sterile medical devices and filling such devices.

SUMMARY

One aspect of the present disclosure provides a wearable drug deliverydevice including a main housing, a container, a drug, a window, a trocaror introducer needle, a cannula, a drive mechanism, an insertionmechanism, a fluid pathway connector, a button, and a trigger assembly.The container may be disposed in the main housing. The container mayinclude a barrel, a plunger seal moveable through the barrel, and afirst pierceable seal controlling access to an interior of the barrel.The drug may be disposed in the barrel. The drug may include at leastone of a: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) specificantibody, a granulocyte colony-stimulating factor (G-CSF), a sclerostinantibody, or a calcitonin gene-related peptide (CGRP) antibody. Thetrocar or introducer needle may have a proximal end and a distal end.The cannula may initially be disposed around the distal end of thetrocar or introducer needle. The drive mechanism may be disposed in themain housing. The drive mechanism may include a drive housing, a pistonmoveable relative to the drive housing and configured to impart movementto the plunger seal, a gear assembly, an electrical actuator, a gearinterface, a piston biasing member, and a tether. The gear interface maybe rotatable by the electrical actuator. Rotation of the gear interfacemay cause the gear interface to selectively engage the gear assembly toprevent or allow rotation of the gear assembly. The piston biasingmember may be disposed between the drive housing and the piston. Thepiston biasing member maybe initially retained in a piston biasingmember energized state. The piston biasing member may be configured tomove the piston as the piston biasing member de-energizes. The tethermay be connected at opposite ends to the gear assembly and the piston.The tether may initially retain the piston biasing member in the pistonbiasing member energized state. Rotation of the gear assembly may createslack in the tether which allows the piston biasing member tode-energize. The fluid pathway connector may define a sterile fluidflowpath between the container and the insertion mechanism. The fluidpathway connector may include a tubular conduit, a container accessneedle, and a connection hub. The tubular conduit may have a first endand a second end. The second end of the tubular conduit may be in fluidcommunication with a hollow interior of the cannula during drugdelivery. The container access needle may be configured to pierce thefirst pierceable seal to establish fluid communication between thebetween the barrel and the tubular conduit during drug delivery. Theconnection hub may be connected to the container access needle and thefirst end of the tubular conduit. The connection hub may provide fluidcommunication between the container access needle and the tubularconduit during drug delivery. The insertion mechanism may be disposed inthe main housing. The insertion biasing mechanism may include a base, aninsertion mechanism housing rotatable relative to the base, a rotationalbiasing member connected to the insertion mechanism housing, a firstretainer, a hub, a retraction biasing member, and a second retainer. Therotational biasing member may be initially retained in a rotationalbiasing member energized state. The rotational biasing member may beconfigured to rotate the insertion mechanism housing as the rotationalbiasing member de-energizes. The first retainer may be moveable between:(i) a first retainer retaining position, where the first retainerretains the rotational biasing member in the rotational biasing memberenergized state, and (ii) a first retainer releasing position, where thefirst retainer allows the rotational biasing member to de-energize. Thehub may be connected to the proximal end of the trocar or introducerneedle, and the hub may be configured to translate relative to theinsertion mechanism housing. The retraction biasing member may bedisposed between the hub and the base. The retraction biasing member mayhave a retraction biasing member energized state. The retraction biasingmember may be configured to translate the hub in a proximal direction asthe retraction biasing member de-energizes. The second retainer may bemoveable between: (i) a second retainer retaining position, where thesecond retainer retains the retraction biasing member in the retractionbiasing member energized state, and (ii) a second retainer releasingposition, where the second retainer allows the retraction biasing memberto de-energize. The button may protrude from the main housing andmanually displaceable by a user. The trigger assembly may be configuredto move the first retainer from the first retainer retaining position tothe first retainer releasing position in response to displacement of thebutton by the user.

Another aspect of the present disclosure provides a wearable drugdelivery device including a container, a drug disposed in the container,a trocar or introducer needle, an activation member manually operable bya patient, an insertion mechanism, a fluid pathway connector, a lockingassembly, and a selector. The drug may include at least one of a:Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) specific antibody,a granulocyte colony-stimulating factor (G-CSF), a sclerostin antibody,or a calcitonin gene-related peptide (CGRP) antibody. The insertionmechanism may be configured to move the trocar or introducer needlebetween a retracted position and an inserted position, the insertionmechanism including a rotatable housing and a rotational biasing memberinitially held in an energized state. The fluid pathway connector maydefine a sterile fluid flowpath between the container and the insertionmechanism. The locking assembly may have: (i) a lock configuration,where the locking assembly engages the rotatable housing to inhibitrotation of the rotatable housing, and (ii) an unlock configuration,where the locking assembly disengages the rotatable housing to permitrotation of the rotatable housing. The selector may have: (i) a firstconfiguration, where the selector operatively decouples the activationmember and the locking assembly, and (ii) a second configuration, wherethe selector operatively couples the activation member and the lockingassembly to allow the activation member to change the locking assemblyfrom the lock configuration to the unlock configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

It is believed that the disclosure will be more fully understood fromthe following description taken in conjunction with the accompanyingdrawings. Some of the figures may have been simplified by the omissionof selected elements for the purpose of more clearly showing otherelements. Such omissions of elements in some figures are not necessarilyindicative of the presence or absence of particular elements in any ofthe exemplary embodiments, except as may be explicitly delineated in thecorresponding written description. Also, none of the drawings isnecessarily to scale.

FIG. 1A shows an isometric view of a drug delivery pump having safetyintegrated insertion mechanisms, according to one embodiment of thepresent invention;

FIG. 1B shows an isometric view of the interior components of the drugdelivery pump shown in FIG. 1A;

FIG. 1C shows an isometric view of the bottom of the drug delivery pumpshown in FIG. 1A;

FIG. 2A shows an isometric view of the interior components of a secondembodiment of a drug delivery device;

FIG. 2B shows a second view of the interior components of the drugdelivery device shown in FIG. 2A;

FIG. 3A is an isometric view of an embodiment of a fluid pathwayconnection assembly and drug container in an unmounted configuration;

FIG. 3B is an isometric view of the embodiment shown in FIG. 3A in amounted, but unactuated, configuration;

FIG. 4A shows an exploded view of a fluid pathway connection assemblyaccording to at least one embodiment of the present invention;

FIG. 4B shows a cross-sectional view of the exploded fluid pathwayconnection assembly of FIG. 4A;

FIG. 5A is a cross-sectional side view of an embodiment of a fluidpathway connection assembly and a drug container in a mounted, butunactuated, configuration;

FIG. 5B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 5A;

FIG. 6A is a cross-sectional side view of the embodiment of the fluidpathway connection assembly and drug container of FIG. 4A in an actuatedconfiguration;

FIG. 6B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 6A;

FIG. 7A is a cross-sectional side view of the embodiment of the fluidpathway connection assembly and drug container of FIGS. 4A and 6A in adelivery configuration;

FIG. 7B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 7A;

FIG. 8 shows an isometric view of a connection hub according to at leastone embodiment of the present invention;

FIG. 9 shows an isometric view of a plate according to at least oneembodiment of the present invention;

FIG. 10 shows an isometric view of an embodiment of a piercing memberretainer according to at least one embodiment of the present invention;

FIG. 11 shows an isometric view of an embodiment of an introducer memberretainer according to at least one embodiment of the present invention;

FIG. 12A is an isometric view of a second embodiment of a fluid pathwayconnection assembly and drug container in an unmounted configuration;

FIG. 12B is an isometric view of the embodiment shown in FIG. 12A in amounted, but unactuated, configuration;

FIG. 13A is a cross-sectional side view of the embodiment of the fluidpathway connection assembly and drug container of FIGS. 11A-11B in amounted, but unactuated, configuration;

FIG. 13B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 13A;

FIG. 14A is a cross-sectional side view of the embodiment of the fluidpathway connection assembly and drug container of FIG. 12A in anactuated configuration;

FIG. 14B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 14A;

FIG. 15A is a cross-sectional side view of the embodiment of the fluidpathway connection assembly and a drug container of FIGS. 12A and 13A ina delivery configuration;

FIG. 15B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 15A;

FIG. 16A is a further isometric view of the fluid pathway connectionassembly and container of FIGS. 12A-12B in a mounted, but unactuated,configuration;

FIG. 16B is an enlarged fragmentary isometric view of the fluid pathwayconnection assembly of FIG. 16A;

FIG. 17A is a further isometric view of the fluid pathway connectionassembly and container of FIGS. 12A-12B in an actuated configuration;

FIG. 17B is an enlarged fragmentary isometric view of the fluid pathwayconnection assembly of FIG. 17A;

FIG. 18A is a further isometric view of the fluid pathway connectionassembly and container of FIGS. 12A-12B in a delivery configuration;

FIG. 18B is an enlarged fragmentary isometric view of the fluid pathwayconnection assembly of FIG. 18A;

FIG. 19A is a bottom side view of the fluid pathway connection assemblyand container of FIG. 18A;

FIG. 19B is an enlarged fragmentary isometric view of the fluid pathwayconnection assembly and drug container of FIG. 19A;

FIG. 20 shows an isometric view of a connection hub according to atleast one embodiment of the present invention;

FIG. 21 shows an isometric view of an embodiment of an introducer memberretainer according to at least one embodiment of the present invention;

FIG. 22 shows an isometric view of an embodiment of a piercing memberretainer according to at least one embodiment of the present invention;

FIG. 23 shows an isometrically exploded view of a fluid pathwayconnection assembly according to at least one embodiment of the presentinvention;

FIG. 24A shows an isometric view of the fluid pathway connectionassembly and drug container of FIG. 23 in an unmounted configuration;

FIG. 24B is an isometric view of the fluid pathway connection assemblyand drug container of FIG. 24A in a mounted, but unactuated,configuration;

FIG. 24C is an isometric view of the fluid pathway connection assemblyand drug container of FIG. 24B in an actuated configuration;

FIG. 24D is an isometric view of the fluid pathway connection assemblyand drug container of FIGS. 24B-24C in a delivery configuration;

FIG. 25A is a cross-sectional side view of the fluid pathway connectionassembly and drug container of FIG. 24B in the mounted, but unactuated,configuration;

FIG. 25B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 25A;

FIG. 26A is a cross-sectional side view of the embodiment of the fluidpathway connection assembly and drug container of FIG. 24B in anactuated configuration;

FIG. 26B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 26A;

FIG. 27A is a cross-sectional side view of the embodiment of the fluidpathway connection assembly and drug container of FIGS. 25A and 26A in adelivery configuration;

FIG. 27B is an enlarged fragmentary cross-sectional side view of theembodiment shown in FIG. 27A;

FIG. 28 shows an isometric view of a connection hub according to atleast one embodiment of the present invention;

FIG. 29 shows a side elevational view of an embodiment of an introducermember retainer according to at least one embodiment of the presentinvention;

FIG. 30 shows an isometric view of an embodiment of a piercing memberretainer according to at least one embodiment of the present invention;

FIG. 31 shows a fragmentary isometric view of the interior components ofa drug delivery pump incorporating the fluid pathway connection assemblyof FIGS. 23-27B;

FIG. 32A is a fragmentary isometric view of a fluid pathway connectionassembly and a drug container of at least one embodiment of the presentinvention during fluid connection;

FIG. 32B is a fragmentary isometric view of the fluid pathway connectionassembly and drug container of FIG. 32A upon disconnection;

FIG. 33A shows an isometric view of the interior components of a drugdelivery device having a multi-function drive mechanism, according toone embodiment of the present disclosure (shown without the adhesivepatch);

FIG. 33B shows an isometric view of the interior components of the drugdelivery device shown in FIG. 33A (shown without the adhesive patch)from another viewpoint;

FIG. 33C shows an isometric view of the interior components of the drugdelivery device shown in FIG. 33A (shown without the adhesive patch)from yet another viewpoint;

FIG. 34A is an isometric view of an embodiment of a fluid pathconnection assembly and drug container in an unmounted configuration;

FIG. 34B is an isometric view of the embodiment shown in FIG. 34A in amounted configuration;

FIG. 34C is a cross-sectional isometric view of the embodiment shown inFIG. 34A in a mounted configuration;

FIG. 35A is an isometric view of an embodiment of a fluid pathconnection assembly and a drug container in an unmounted configuration;

FIG. 35B is an isometric view of the embodiment shown in FIG. 35A in amounted configuration;

FIG. 35C is a cross-sectional isometric view of the embodiment shown inFIG. 35A in a mounted configuration;

FIG. 35D is a cross-sectional isometric view of the embodiment shown inFIG. 35A after connection of the fluid path;

FIG. 36A is a cross-sectional side view of an embodiment of a fluid pathconnection assembly and a drug container in an mounted configuration;

FIG. 36B is a cross-sectional side view of the embodiment shown in FIG.36A after the first and second films have been pierced;

FIG. 36C is a cross-sectional side view of the embodiment shown in FIG.36A after retraction of the outer piercing member;

FIG. 36D is a cross-sectional side view of the embodiment shown in FIG.36A after connection of the fluid path;

FIG. 37A is a cross-sectional side view of an embodiment of a fluid pathconnection mechanism and a drug container in an unmounted configuration;

FIG. 37B is a cross-sectional side view of the embodiment shown in FIG.37A after piercing of the first and second films by the outer piercingmember;

FIG. 37C is a cross-sectional side view of the embodiment shown in FIG.37A after connection of the fluid path;

FIG. 38A is a cross-sectional side view of an embodiment of a fluid pathconnection mechanism and a drug container in an unmounted configuration;

FIG. 38B is a cross-sectional side view of the embodiment shown in FIG.38A in a mounted configuration;

FIG. 38C is a cross-sectional side view of the embodiment shown in FIG.38A after piercing of the first and second films by the outer piercingmember;

FIG. 38D is a cross-sectional side view of the embodiment shown in FIG.38A after connection of the fluid path;

FIG. 39A is a cross-sectional side view of an embodiment of a fluid pathconnection mechanism and a drug container in a mounted configuration;

FIG. 39B is a cross-sectional side view of the embodiment of FIG. 39Aafter connection of the fluid path;

FIG. 40A is a cross-sectional side view of an embodiment of a fluid pathconnection mechanism and a drug container in an unmounted configuration;

FIG. 40B is a cross-sectional side view of the embodiment shown in FIG.40A in a mounted configuration;

FIG. 40C is a cross-sectional side view of the embodiment shown in FIG.40A after connection of the fluid path;

FIG. 41A is a cross-sectional side view of an embodiment of a fluid pathconnection mechanism and a drug container in an unmounted configuration;

FIG. 41B is a cross-sectional side view of the embodiment shown in FIG.41A in a mounted configuration;

FIG. 41C is a cross-sectional side view of the embodiment shown in FIG.41A during UV sterilization;

FIG. 41D is a cross-sectional side view of the embodiment shown in FIG.41A after connection of the fluid path;

FIG. 42 shows a fluid path connection according to at least oneembodiment of the present disclosure;

FIG. 43 shows an isometric view of a drug container according to atleast one embodiment of the present disclosure;

FIG. 44 shows an isometric view of a drug container and a fluid pathwayconnection according to at least one embodiment of the presentdisclosure;

FIG. 45A shows an isometric view of the drug container and fluid pathwayconnection of FIG. 44 in an unmounted configuration;

FIG. 45B shows a cross-sectional isometric view of the drug containerand fluid pathway connection of FIG. 44 in an initial mountingconfiguration;

FIG. 45C shows a cross-sectional isometric view of the drug containerand fluid pathway connection of FIG. 44 in an intermediate mountingconfiguration;

FIG. 45D shows a cross-sectional isometric view of the drug containerand fluid pathway connection of FIG. 44 in a mounted configuration;

FIG. 46A shows an isometric view of an embodiment of a drug containerand fluid pathway connection in an unmounted configuration;

FIG. 46B shows a cross-sectional isometric view of the drug containerand fluid pathway connection of FIG. 46A in a mounted configuration;

FIG. 47 shows a detail cross-sectional view of a fluid pathwayconnection according to at least one embodiment of the presentdisclosure;

FIG. 48 shows a cross-sectional isometric view of an embodiment of adrug container and fluid pathway connection in an unmountedconfiguration;

FIG. 49 shows an isometric view of an embodiment of a drug container andfluid pathway connection in an unmounted configuration;

FIG. 50 shows a cross-sectional view of an embodiment of a drugcontainer and fluid pathway connection in an unmounted configuration;

FIG. 51 shows a cross-sectional isometric view of an embodiment of adrug container and fluid pathway connection in an unmountedconfiguration;

FIG. 52A shows an isometric view of an embodiment of a drug containerand fluid pathway connection in an unmounted configuration;

FIG. 52B shows an end view of a drug container;

FIG. 52C shows a cross-sectional view of a drug container and fluidpathway connection in an unmounted configuration;

FIG. 52D shows a cross-sectional view of a drug container and fluidpathway connection in a connected configuration;

FIG. 53A is an isometric view of an integrated sterile fluid pathwayconnection and drug container, according to an embodiment;

FIG. 53B is a sectional isometric view of the integrated sterile fluidpathway connection and drug container shown in FIG. 53A;

FIG. 54A is an exploded, side view of the components of an embodiment ofan integrated sterile fluid pathway connection and drug container,exploded along a longitudinal axis;

FIG. 54B is a sectional exploded view of the embodiment of FIG. 54A;

FIG. 55A is a sectional view of an integrated sterile fluid pathwayconnection and drug container, as shown in FIG. 53A, prior to useractivation;

FIG. 55B is a sectional view of the embodiment with the fluid pathwayconnected; and FIG. 55C is a sectional view of the embodiment at the endof drug delivery;

FIG. 56A is an isometric perspective view, of the integrated sterilefluid pathway connection according to an embodiment of the presentinvention;

FIG. 56B is an exploded, perspective view of the components of theintegrated sterile fluid pathway connection shown in FIG. 56A;

FIG. 57A is a sectional view of an embodiment of an integrated sterilefluid pathway connection, having a piercing member guide and drugcontainer, prior to user activation;

FIG. 57B shows an isometric perspective view of the piercing memberguide and piercing member of the embodiment shown in FIG. 57A; and FIG.57C is an isometric view of the piercing member guide, piercing member,and connector hub of the embodiment of FIG. 57A;

FIG. 58 is a cross-sectional view of an integrated sterile fluid pathwayconnection and drug container according to an embodiment prior to useractivation, in which the drug container comprises more than one drugchamber, each drug chamber separated from the next by a pierceablemembrane;

FIG. 59A to FIG. 59E are sectional views of an embodiment of a sterilefluid connector in which the pierceable seal is configured to maintaindifferent positions within the connector in response to pneumatic and/orhydraulic pressure;

FIG. 60A to FIG. 60H are sectional and isometric sectional views of anembodiment of a sterile fluid connector in which the pierceable seal, inresponse to pneumatic and/or hydraulic pressure, engages or disengages asensor mechanism that is capable of transmitting a signal indicating thestatus of fluid transfer from the sterile fluid container to theconnector;

FIG. 61A to FIG. 61G are perspective and sectional views of anotherembodiment of a sterile fluid connector capable of transmitting a signalindicating the status of fluid transfer from the sterile fluid containerto the connector;

FIG. 62A to FIG. 62D are sectional and isomeric sectional views ofanother embodiment of a sterile fluid connector capable of transmittinga signal indicating the status of fluid transfer from the sterile fluidcontainer to the connector, showing more specific configurations of asensor in the open and closed positions;

FIG. 63A to FIG. 63D are perspective and sectional views of anembodiment of a sterile fluid connector capable of transmitting a signalindicating the status of fluid transfer from the sterile fluid containerto the connector, illustrating the unpressurized (FIG. 63B), pressurized(FIG. 63C), and end-of-delivery (FIG. 63D) positions of components of asterile fluid connector;

FIG. 64A to FIG. 64C are perspective and sectional views of anotherembodiment of a sterile fluid connector capable of transmitting a signalindicating the status of fluid transfer from the sterile fluid containerto the connector;

FIG. 65A is a sectional view and FIG. 65B is an isometric sectional viewof another embodiment of a sterile fluid connector capable oftransmitting a signal indicating the status of fluid transfer from thesterile fluid container to the connector;

FIG. 66A and FIG. 66B are sectional isometric views of anotherembodiment of a sterile fluid connector capable of transmitting a signalindicating the status of fluid transfer from the sterile fluid containerto the connector, in which the pierceable seal comprises a conductivematerial or coating;

FIG. 67 is a sectional isometric view of another an embodiment of asterile fluid connector capable of transmitting a signal indicating thestatus of fluid transfer from the sterile fluid container to theconnector, in which signal is mediated using an conductive elastomericfilm;

FIG. 68 is a sectional isometric view of another embodiment of a sterilefluid connector capable of transmitting a signal indicating the statusof fluid transfer from the sterile fluid container to the connector, inwhich signal is mediated using a dome switch;

FIG. 69A shows an isometric view of the interior components of a drugdelivery pump having a multi-function drive mechanism, according to oneembodiment of the present invention (shown without the adhesive patch);

FIG. 69B shows an isometric view of the interior components of the drugdelivery pump shown in FIG. 69A (shown without the adhesive patch) fromanother viewpoint;

FIG. 69C shows an isometric view of the interior components of the drugdelivery pump shown in FIG. 69A (shown without the adhesive patch) fromyet another viewpoint;

FIG. 69D shows a top view, along an axis “A,” of the interior componentsof the drug delivery pump shown in FIG. 69A;

FIG. 70A shows an isometric view of a multi-function drive mechanism,according to at least one embodiment of the present invention prior toactivation;

FIG. 70B shows an isometric view of a multi-function drive mechanism,according to at least one embodiment of the present invention duringactivation;

FIG. 70C shows an isometric view of a multi-function drive mechanism,according to at least one embodiment of the present invention at a laterstage during activation;

FIG. 70D shows an isometric view of a multi-function drive mechanism,according to at least one embodiment of the present invention near or atcompletion of drug delivery;

FIGS. 71A-71D show top views which correspond with the stages ofoperation shown in FIGS. 70A-70D, respectively;

FIG. 72 shows the multi-function drive mechanism, according to at leastone embodiment of the present invention, in isolation from the drugdelivery device;

FIGS. 73A-73B show top and bottom views, respectively, of themulti-function drive mechanism shown in FIG. 72;

FIGS. 73C-73D show front and back perspective views, respectively, ofthe multi-function drive mechanism shown in FIG. 72;

FIG. 74A shows a cross-sectional view of a drug container and safetymechanism in an initial, unrestrained configuration;

FIG. 74B shows a cross-sectional view of the drug container and safetymechanism of FIG. 74A in an activated configuration;

FIG. 75A shows an isometric view of a drug delivery pump in which theinsertion mechanism includes a rotational biasing member;

FIG. 75B shows an enlarged view of the drive mechanism shown in FIG.75A.

FIG. 76A is an exemplary block diagram illustrating one embodiment of apower and control system of the drug delivery pump;

FIG. 76B is an exemplary block diagram depicting one embodiment of adrive control system of the drug delivery pump;

FIG. 76C is an exemplary block diagram of an embodiment illustratingvarious control mechanisms of the drug delivery pump;

FIG. 76D is an exemplary block diagram of another embodimentillustrating communication among an exemplary drug delivery pump device,an exemplary mobile device, an exemplary cloud server and one or moreexemplary sensors;

FIGS. 77A-77C are flow-charts of embodiments describing methods of drugdelivery by the drug delivery device based on one or more mechanisms;

FIG. 78A is an exemplary block diagram illustrating one embodiment of apower and control system of the drug delivery pump;

FIG. 78B is an exemplary block diagram depicting one embodiment of adrive control system of the drug delivery pump;

FIG. 78C is an exemplary block diagram of an embodiment illustratingvarious control mechanisms of the drug delivery pump;

FIGS. 79A-79B are flow-charts of embodiments describing methods of drugdelivery by the drug delivery device based on one or more mechanisms;

FIG. 80A shows an isometric view of a drug delivery pump having acontrolled delivery drive mechanism, according to one embodiment of thepresent invention;

FIG. 80B shows an isometric view of the interior components of the drugdelivery pump shown in FIG. 80A (shown without the adhesive patch);

FIG. 80C shows an isometric view of the bottom of the drug delivery pumpshown in FIG. 80A (shown without the adhesive patch);

FIG. 81A shows an exploded view, along an axis “A,” of a drive mechanismand drug container, of one embodiment of the present invention;

FIG. 81B shows an exploded view, along an axis “B,” of one embodiment ofthe present invention (biasing member, cover sleeve, plunger seal,barrel, and cap are not shown for clarity);

FIG. 82A shows an isometric view of a controlled delivery drivemechanism, according to at least one embodiment of the presentinvention;

FIG. 82B shows an isometric view of a controlled delivery drivemechanism, according to at least one embodiment of the present invention(the piston is shown exploded to illustrate attachment of tether);

FIGS. 83A-83C shows an enlarged view of an escapement regulatingmechanism of a drive mechanism, according to at least one embodiment ofthe present invention;

FIGS. 83D-83H shows the progression of the escapement regulatingmechanism, according to the embodiment shown in FIGS. 83A-83C, duringoperation;

FIG. 84A shows an isometric view of the drive mechanism and drugcontainer shown in FIG. 81 in an initial inactive state;

FIG. 84B shows an isometric view of the drive mechanism shown in FIG. 81as the mechanism completes drug delivery;

FIG. 85A shows a cross-sectional view of the drive mechanism shown inFIG. 81 in an initial inactive state;

FIG. 85B shows a cross-sectional view of the drive mechanism shown inFIG. 81 in an actuated state as the mechanism controls the rate orprofile of drug delivery;

FIG. 85C shows a cross-sectional view of the drive mechanism shown inFIG. 81 as the mechanism completes drug delivery and, optionally,performs a compliance push to ensure completion of drug delivery;

FIG. 86A shows an isometric view of a drug delivery pump having acontrolled delivery drive mechanism, according to one embodiment of thepresent invention;

FIG. 86B shows an isometric view of the interior components of the drugdelivery pump shown in FIG. 86A (shown without the adhesive patch);

FIG. 86C shows an isometric view of the bottom of the drug delivery pumpshown in FIG. 86A (shown without the adhesive patch);

FIG. 87 shows an isometric view of a controlled delivery drivemechanism, according to at least one embodiment of the presentinvention;

FIG. 88 shows an exploded view, along an axis “A,” of the drivemechanism shown in FIG. 87 (but excluding the plunger seal, barrel, andcap for clarity);

FIG. 89A shows an isometric view of the drive mechanism shown in FIG. 87in an initial inactive state;

FIG. 89B shows an isometric view of the drive mechanism shown in FIG. 87in an actuated state as the mechanism controls the rate or profile ofdrug delivery;

FIG. 89C shows an isometric view of the drive mechanism shown in FIG. 87as the mechanism completes drug delivery;

FIG. 90A shows a cross-sectional view of the drive mechanism shown inFIG. 89A in an initial inactive state;

FIG. 90B shows a cross-sectional view of the drive mechanism shown inFIG. 89B in an actuated state as the mechanism controls the rate orprofile of drug delivery;

FIG. 90C shows a cross-sectional view of the drive mechanism shown inFIG. 89C as the mechanism completes drug delivery and, optionally,performs a compliance push to ensure completion of drug delivery;

FIG. 91 shows a perspective view of the drive mechanism whichincorporates an incremental status indicator, according to a furtherembodiment of the present invention;

FIG. 92A shows an isometric view of a drug delivery pump having avariable rate controlled delivery drive mechanism, according to oneembodiment of the present invention;

FIG. 92B shows an isometric view of the interior components of the drugdelivery pump shown in FIG. 92A (shown without the adhesive patch);

FIG. 92C shows an isometric view of the bottom of the drug delivery pumpshown in FIG. 92A (shown without the adhesive patch);

FIG. 93 shows an isometric view of a controlled delivery drivemechanism, according to at least one embodiment of the presentinvention;

FIG. 94A shows a partially exploded view, along an axis “A,” of thedrive mechanism shown in FIG. 93;

FIG. 94B shows a fully exploded view, along an axis “A” and along aperpendicular axis “B”, of certain components of the drive mechanismshown in FIG. 93;

FIGS. 95A-95C shows an enlarged view of an escapement regulatingmechanism of a drive mechanism, according to at least one embodiment ofthe present invention;

FIGS. 95D-95H shows the progression of the escapement regulatingmechanism, according the embodiment shown in FIGS. 95A-95C, duringoperation;

FIG. 96A shows an isometric view of the drive mechanism shown in FIG. 93in an initial inactive state;

FIG. 96B shows an isometric view of the drive mechanism shown in FIG. 93in an actuated state as the mechanism controls the rate or profile ofdrug delivery;

FIG. 96C shows an isometric view of the drive mechanism shown in FIG. 93as the mechanism completes drug delivery;

FIG. 97A shows a cross-sectional view of the drive mechanism shown inFIG. 96A in an initial inactive state;

FIG. 97B shows a cross-sectional view of the drive mechanism shown inFIG. 96B in an actuated state as the mechanism controls the rate orprofile of drug delivery;

FIG. 97C shows a cross-sectional view of the drive mechanism shown inFIG. 96C as the mechanism completes drug delivery and, optionally,performs a compliance push to ensure completion of drug delivery;

FIG. 98 shows an isometric view of a controlled delivery drive mechanismwhich incorporates a status indicator, according to at least oneembodiment of the present invention;

FIG. 99 shows an isometric view of a controlled delivery drive mechanismaccording to another embodiment of the present invention;

FIG. 100A shows an isometric view of a drug delivery pump having avariable rate controlled delivery drive mechanism, according to oneembodiment of the present invention;

FIG. 100B shows an isometric view of the interior components of the drugdelivery pump shown in FIG. 100A (shown without the adhesive patch);

FIG. 100C shows an isometric view of the bottom of the drug deliverypump shown in FIG. 100A (shown without the adhesive patch);

FIG. 101 shows an isometric view of a variable rate controlled deliverydrive mechanism, according to at least one embodiment of the presentinvention;

FIG. 102 shows an exploded view, along an axis “A,” of the drivemechanism shown in FIG. 101;

FIG. 103A shows an isometric cross-sectional view of the drive mechanismshown in FIG. 101 in an initial inactive state;

FIG. 103B shows an isometric cross-sectional view of the drive mechanismshown in FIG. 101 in an actuated state as the mechanism controls therate or profile of drug delivery;

FIG. 103C shows an isometric cross-section view of the drive mechanismshown in FIG. 101 as the mechanism completes drug delivery;

FIG. 104A shows a cross-sectional view of the drive mechanism shown inFIG. 103A in an initial inactive state;

FIG. 104B shows a cross-sectional view of the drive mechanism shown inFIG. 103B in an actuated state as the mechanism controls the rate orprofile of drug delivery;

FIG. 104C shows a cross-sectional view of the drive mechanism shown inFIG. 103C as the mechanism completes drug delivery and, optionally,performs a compliance push to ensure completion of drug delivery;

FIG. 105 shows an isometric view of a variable rate controlled deliverydrive mechanism, according to another embodiment of the presentinvention;

FIG. 106 shows an exploded view, along an axis “A,” of the drivemechanism shown in FIG. 105;

FIG. 107A shows an isometric cross-sectional view of the drive mechanismshown in FIG. 105 in an initial inactive state;

FIG. 107B shows an isometric cross-sectional view of the drive mechanismshown in FIG. 105 in an actuated state as the mechanism controls therate or profile of drug delivery;

FIG. 107C shows an isometric cross-sectional view of the drive mechanismshown in FIG. 105 as the mechanism completes drug delivery;

FIG. 108A shows a cross-sectional view of the drive mechanism shown inFIG. 107A in an initial inactive state;

FIG. 108B shows a cross-sectional view of the drive mechanism shown inFIG. 107B in an actuated state as the mechanism controls the rate orprofile of drug delivery;

FIG. 108C shows a cross-sectional view of the drive mechanism shown inFIG. 107C as the mechanism completes drug delivery and, optionally,performs a compliance push to ensure completion of drug delivery;

FIG. 109A shows an isometric view of a variable rate controlled deliverydrive mechanism which incorporates a mechanical status indicator,according to a further embodiment of the present invention;

FIG. 109B shows an isometric view of a variable rate controlled deliverydrive mechanism which incorporates an optical status indicator,according to yet another embodiment of the present invention;

FIG. 110A is an isometric view of a drug delivery pump having a drivemechanism, according to one embodiment of the present invention (shownwithout the adhesive patch);

FIG. 110B is an isometric view of the interior components of the drugdelivery pump shown in FIG. 110A (shown without the adhesive patch);

FIG. 110C is an isometric view of the drug delivery pump shown in FIG.110A (shown without the adhesive patch) from yet another viewpoint;

FIG. 111A is a top view, along an axis “A,” of the interior componentsof an exemplary drug delivery pump;

FIG. 111B is an isometric view of a drive mechanism, according to atleast one embodiment of the present invention prior to activation;

FIG. 111C is an isometric view of a drive mechanism, according to atleast one embodiment of the present invention during activation;

FIG. 111D is an isometric view of a drive mechanism, according to atleast one embodiment of the present invention at a later stage duringactivation;

FIG. 111E is an isometric view of a drive mechanism, according to atleast one embodiment of the present invention near or at completion ofdrug delivery;

FIGS. 112A-112D are top views which correspond with the stages ofoperation shown in FIGS. 111A-111E, respectively;

FIG. 113 is an isometric view of the drive mechanism, according to atleast one embodiment of the present invention, in isolation from thedrug delivery device;

FIGS. 114A-114B are top and bottom views, respectively, of the drivemechanism shown in FIG. 113;

FIGS. 114C-114D are front and back perspective views, respectively, ofthe drive mechanism shown in FIG. 113;

FIG. 115A is an isometric view of a drug delivery pump in which theinsertion mechanism includes a rotational biasing member;

FIG. 115B is an enlarged view of the drive mechanism shown in FIG. 115A

FIG. 116A is an isometric view of an insertion mechanism in an initialconfiguration;

FIG. 116B is an enlarged, fragmentary isometric view of the insertionmechanism of FIG. 116A;

FIG. 117A is a side elevation view of the insertion mechanism of FIG.116A in an initial configuration;

FIG. 117B is an enlarged, fragmentary, side elevation view of theinsertion mechanism of FIG. 117A;

FIG. 118A is an isometric view of the insertion mechanism of FIG. 116Ain an intermediate configuration;

FIG. 118B is an enlarged, fragmentary isometric view of the insertionmechanism of FIG. 118A;

FIG. 119A is a side elevation view of the insertion mechanism of FIG.118A in an intermediate configuration;

FIG. 119B is an enlarged, fragmentary, side elevation view of theinsertion mechanism of FIG. 119A;

FIG. 120A is an isometric view of the insertion mechanism of FIG. 116Ain an released configuration;

FIG. 120B is an enlarged, fragmentary isometric view of the insertionmechanism of FIG. 120A;

FIG. 121A is a side elevation view of the insertion mechanism of FIG.120A in an released configuration;

FIG. 121B is an enlarged, fragmentary, side elevation view of theinsertion mechanism of FIG. 121A;

FIG. 122A is a side elevation view of an enabling mechanism according toat least one embodiment of the present invention;

FIG. 122B is an enlarged, fragmentary side elevation view of theenabling mechanism of FIG. 122A;

FIG. 123 is an isometric view of a regulating mechanism according to atleast one embodiment of the present invention;

FIGS. 124A-124B are isometric views of a key according to at least oneembodiment of the present invention;

FIG. 124C is an isometric views of a key according to another embodimentof the present invention;

FIG. 125 is a plan view of a main gear according to at least oneembodiment of the present invention;

FIG. 126A is an isometric view of a drive mechanism according to oneembodiment of the invention in a first configuration;

FIG. 126B is an enlarged, fragmentary, isometric view of the drivemechanism of FIG. 126A in the first configuration;

FIG. 127A is an isometric view of the drive mechanism of FIG. 126A in asecond configuration;

FIG. 127B is an enlarged, fragmentary, isometric view of the drivemechanism of FIG. 127A in the second configuration;

FIG. 128A is an isometric view of the drive mechanism of FIG. 126A in athird configuration;

FIG. 128B is an enlarged, fragmentary, isometric view of the drivemechanism of FIG. 128A in the third configuration;

FIG. 129A is an isometric view of the drive mechanism of FIG. 126A in afourth configuration;

FIG. 129B is an enlarged, fragmentary, isometric view of the drivemechanism of FIG. 129A in the fourth configuration;

FIG. 130A is an isometric view of one embodiment of a winch drum andwinch gear in a first configuration;

FIG. 130B is an isometric view of the winch drum and winch gear of FIG.130A in a second configuration;

FIG. 131 is an isometric view of a winch gear of the embodiment of FIGS.130A-131B;

FIG. 132 is an isometric view of a coupler of a winch drum of theembodiment of FIGS. 131A-131B;

FIG. 133 is an isometric view of a capstan of a winch drum of theembodiment of FIGS. 130A-130B;

FIG. 134A is a cross-sectional view of a safety mechanism according toone embodiment of the invention in an initial configuration;

FIG. 134B is an enlarged, fragmentary, cross-sectional view of thesafety mechanism of FIG. 134A in an initial configuration;

FIG. 135A is a cross-sectional view of a safety mechanism of FIG. 134Ain an actuated configuration;

FIG. 135B is an enlarged, fragmentary, cross-sectional view of thesafety mechanism of FIG. 135A in the actuated configuration;

FIG. 136A is a cross-sectional view of a safety mechanism of FIG. 134Ain a retracted configuration;

FIG. 136B is an enlarged, fragmentary, cross-sectional view of thesafety mechanism of FIG. 136A in the retracted configuration;

FIGS. 137A-137B are cross-sectional views of a safety mechanismaccording to another embodiment of the present invention;

FIG. 138 is an isometric view according to one embodiment of a springretainer for the safety mechanism of FIGS. 137A-137B;

FIG. 139 is an isometric view according to another embodiment of aspring retainer for the safety mechanism of FIGS. 137A-137B;

FIG. 140 is an isometric view of a sleeve for the safety mechanism ofFIGS. 137A-137B;

FIG. 141A is a fragmentary cross-sectional view of a drug container andsafety mechanism in an initial, unrestrained configuration; and

FIG. 141B is a fragmentary cross-sectional view of the drug containerand safety mechanism of FIG. 141A in an activated configuration;

FIG. 142A shows an exploded view, exploded along an axis “A,” of aninsertion mechanism according to at least one embodiment of the presentdisclosure;

FIG. 142B shows a cross-sectional exploded view, exploded along an axis“A,” of an insertion mechanism according to at least one embodiment ofthe present disclosure;

FIG. 143A shows an isometric view of an insertion mechanism housingaccording to at least one embodiment of the present disclosure;

FIG. 143B shows a cross-section view of the insertion mechanism housingshown in FIG. 143A;

FIG. 144 shows an isometric view of a hub according to at least oneembodiment of the present disclosure;

FIG. 145 shows an isometric view of a sleeve according to at least oneembodiment of the present disclosure;

FIG. 146 shows an embodiment of a base of an insertion mechanismaccording to at least one embodiment of the present disclosure;

FIG. 147A shows an isometric view of an insertion mechanism according toat least one embodiment of the present disclosure in an initialconfiguration;

FIG. 147B shows a cross-sectional view of an insertion mechanismaccording to at least one embodiment of the present disclosure in aninitial configuration;

FIG. 148A shows an isometric view of an insertion mechanism according toat least one embodiment of the present disclosure in a needle insertedconfiguration;

FIG. 148B shows a cross-sectional view of an insertion mechanismaccording to at least one embodiment of the present disclosure in aneedle inserted configuration;

FIG. 149A shows an isometric view of an insertion mechanism according toat least one embodiment of the present disclosure in a needle retractedconfiguration;

FIG. 149B shows a cross-sectional view of an insertion mechanismaccording to at least one embodiment of the present disclosure in aneedle retracted configuration;

FIG. 150 shows an isometric view of an insertion mechanism according toat least one embodiment of the present disclosure;

FIG. 151 shows a cross-sectional side view of the embodiment of FIG.150;

FIG. 152 shows a cross-sectional front view of the embodiment of FIG.150;

FIG. 153A shows a cross-sectional view of an insertion mechanismaccording to at least one embodiment of the present invention in aninitial configuration;

FIG. 153B shows a cross-sectional view of the insertion mechanism ofFIG. 153A in an inserted configuration;

FIG. 153C shows a cross-sectional view of the insertion mechanism ofFIG. 153A in a delivery configuration;

FIG. 154A shows a cross-sectional side elevational view of an insertionmechanism housing according to at least one embodiment of the presentinvention;

FIG. 154B shows a cross-sectional isometric view of the insertionmechanism housing of FIG. 154A;

FIG. 155A is an enlarged, fragmentary cross-sectional view of theinsertion mechanism of FIGS. 153A-153C, while in a deliveryconfiguration;

FIG. 155B is an enlarged, fragmentary cross-sectional view of theinsertion mechanism of FIGS. 153A-153C, while in a retracted position

FIG. 156A shows a cross-sectional view of an insertion mechanismaccording to at least one embodiment of the present invention in aninitial configuration;

FIG. 156B shows a cross-sectional view of the insertion mechanism ofFIG. 156A in an inserted configuration;

FIG. 156C shows a cross-sectional view of the insertion mechanism ofFIG. 156A having the needle hub in a partially-retracted configuration;

FIG. 156D shows a cross-sectional view of the insertion mechanism ofFIG. 156A having the needle hub in a fully-retracted configuration;

FIG. 157A shows a cross-sectional view of the insertion mechanism ofFIG. 156A in an initial configuration taken at 45° rotation to the viewof FIG. 156A;

FIG. 157B shows a cross-sectional view of the insertion mechanism ofFIG. 157A in an inserted configuration;

FIG. 157C shows a cross-sectional view of the insertion mechanism ofFIG. 157A having the needle hub in a retracted configuration;

FIG. 158A shows a cross-sectional view of the insertion mechanism ofFIGS. 156A and 157A in an initial configuration taken at 270° rotationto the view of FIG. 157A;

FIG. 158B shows a cross-sectional view of the insertion mechanism ofFIG. 158A in an inserted configuration;

FIG. 158C shows a cross-sectional view of the insertion mechanism ofFIG. 158A having the needle hub in a retracted configuration;

FIG. 159 is an isometric view of a clip illustrated in FIGS. 156A-158C;

FIG. 160 is an isometric view of a cannula retainer illustrated in FIGS.156A-158C;

FIG. 161 is an isometric view of a needle hub illustrated in FIGS.156A-158C;

FIG. 162 is cross-sectional isometric view of a housing illustrated inFIGS. 156A-158C;

FIG. 163A is an isometric view of a NIM activation mechanism accordingto at least one embodiment of the present invention in an initialconfiguration;

FIG. 163B is an isometric view of the NIM activation mechanism of FIG.163A in an activated configuration;

FIG. 164A is a top view of a NIM retraction mechanism according to atleast one embodiment of the present invention in a deliveryconfiguration;

FIG. 164B is a top view of the NIM retraction mechanism of FIG. 164A ina retracted configuration;

FIG. 165 is an isometric view of a drug delivery device incorporating anembodiment of a fill-finish cartridge according to aspects of thedisclosure;

FIG. 166A is a schematic representation of an exemplary fill-finishcartridge of the present disclosure;

FIG. 166B is a chart of exemplary combinations of components of afill-finish cartridge according to aspects of the disclosure;

FIG. 167 is an exploded isometric view of a fill-finish cartridge,according to an embodiment of the disclosure;

FIG. 168 is an enlarged fragmentary isometric cross-sectional view ofthe fluid pathway connector of the fill-finish cartridge shown in FIG.167, cross-hatching being eliminated for the purposes of clarity;

FIG. 169 is an isometric view of the fill-finish cartridge of FIG. 167before insertion of a plunger seal, elements of FIG. 169 being shown inpartial transparency;

FIG. 170 is an isometric view of the fill-finish cartridge of FIG. 167after insertion of a plunger seal, elements of FIG. 30 being shown inpartial transparency;

FIG. 171 is an exploded isometric view of a tray which may be utilizedto retain a plurality of fill-finish cartridges for use in a fill-finishprocess, elements of FIG. 170 being shown in partial transparency;

FIG. 172 is an isometric view of the a tray of FIG. 171 in an assembledform and holding a plurality of fill-finish cartridges for use in afill-finish process;

FIG. 173 is a side elevational view of another embodiment of afill-finish cartridge, wherein the cartridge includes a fully disposablecarrier;

FIG. 174 is an exploded view of the fill-finish cartridge of FIG. 173;

FIG. 175 is a cross-sectional view of the fill-finish cartridge of FIGS.173 and 174, cross-hatching being eliminated for the purposes ofclarity;

FIG. 176 is a side elevational view of the fill-finish cartridge ofFIGS. 173-175 with the carrier removed;

FIG. 177 is an isometric view of a drug delivery device incorporatinganother embodiment of a fill-finish cartridge according to thedisclosure, a portion of a housing of the drug delivery device beingremoved;

FIG. 178 is a side elevational view of the fill-finish cartridge of FIG.177 prior to placement in the housing, and including partiallydisposable carrier;

FIG. 179 is a cross-sectional view of the fill-finish cartridge of FIG.177, cross-hatching being eliminated for the purposes of clarity;

FIG. 180 is a side elevational view of another embodiment of afill-finish cartridge in an assembled configuration;

FIG. 181 is a cross-sectional view of the fill-finish cartridge of FIG.180, cross-hatching being eliminated for the purposes of clarity;

FIG. 182 is a partially exploded view of the fill-finish cartridge ofFIGS. 180 and 181, showing a fluid conduit in the final configuration;

FIG. 183 is an exploded view of the fluid pathway connector of thefill-finish cartridge of FIGS. 180-182;

FIG. 184 is a cross-sectional view of the fill-finish cartridge of FIG.180 similar to the view of FIG. 181, but prior to the coupling of thefluid pathway connector to the needle insertion mechanism,cross-hatching being eliminated for the purposes of clarity;

FIG. 185 is a side elevational view of another embodiment of afill-finish cartridge in an assembled configuration;

FIG. 186 is a cross-sectional view of the fill-finish cartridge of FIG.181, cross-hatching being eliminated for the purposes of clarity;

FIG. 187 is a cross-sectional view of the fill-finish cartridge of FIG.181 similar to the view of FIG. 182, but prior to the coupling of thefluid pathway connector to the needle insertion mechanism,cross-hatching being eliminated for the purposes of clarity;

FIG. 188 is a schematic illustration of a drug delivery device includinga temperature control system, according to one embodiment of the presentdisclosure;

FIG. 189A illustrates an embodiment of an adhesive patch for a drugdelivery device constructed in accordance with principles of the presentdisclosure;

FIG. 189B illustrates an embodiment of an adhesive patch for a drugdelivery device constructed in accordance with principles of the presentdisclosure;

FIG. 190 depicts an embodiment of a non-adhesive patch liner incombination with a drug delivery device constructed in accordance withprinciples of the present disclosure;

FIG. 191A illustrates an exploded assembly view of an embodiment of anadhesive patch for a drug delivery device constructed in accordance withprinciples of the present disclosure;

FIG. 191B depicts the adhesive patch of FIG. 191A in an assembled form;

FIG. 192 illustrates an isometric view of a drug delivery deviceincluding an adhesive patch with stiffening members, according to oneembodiment of the present disclosure;

FIG. 193 illustrates a bottom view an embodiment of a non-adhesive patchliner;

FIG. 194A-194C illustrate a process of attaching the drug deliverydevice of FIG. 192 to a patient's skin;

FIG. 195 is a schematic diagram of a drug delivery device incommunication with a data processing network according to one embodimentof the present disclosure;

FIGS. 196A-196C are schematic diagrams illustrating the operation of anenergy management system according to one embodiment of the presentdisclosure;

FIGS. 197A-197C are schematic diagrams illustrating the operation of anenergy management system according to another embodiment of the presentdisclosure;

FIGS. 198A-198C are schematic diagrams illustrating the operation of anenergy management system according to another embodiment of the presentdisclosure;

FIG. 199 is an isometric view of an energy management system accordingto another embodiment of the present disclosure;

FIG. 200 is an isometric view of an energy management system accordingto another embodiment of the present disclosure;

FIG. 201A shows an exploded view of a medical device with an integratedstimulant source according to at least one embodiment of the presentinvention;

FIG. 201B shows the medical device of the embodiment of FIG. 201Aapplied to a patient's skin and the stimulant source activated;

FIG. 201C shows the medical device of the embodiment of FIG. 201A afterremoval from the patient's skin;

FIG. 202A shows an exploded view of a medical device with an externalstimulant source according to at least one embodiment of the presentinvention;

FIG. 202B shows the medical device of the embodiment of FIG. 202Aapplied to a patient's skin;

FIG. 202C shows the medical device of the embodiment of FIG. 202A afterremoval of the body of the medical device and the stimulant sourceactivated;

FIG. 202D illustrates removal of the adhesive from the patient's skin;

FIG. 203A is a cross-sectional view of an embodiment of a fluid pathwayconnector and drug container prior to drug delivery;

FIG. 203B is a cross-sectional view of the embodiment of a fluid pathwayconnector and drug container of FIG. 203A during drug delivery; and

FIG. 203C is a cross-sectional view of the embodiment of a fluid pathwayconnector and drug container of FIG. 203A following completion of drugdelivery.

DETAILED DESCRIPTION

The present disclosure provides drug delivery devices havingadvantageous insertion mechanisms, drive mechanisms, sterile fluidpathway assemblies, status indicators, safety features, and otheradvantageous components. Such drug delivery devices are safe and easy touse, and are aesthetically and ergonomically appealing forself-administering patients. The drug delivery devices described hereinincorporate features which make activation, operation, and lock-out ofthe drug delivery device simple for even untrained patients. The drugdelivery devices of the present disclosure provide these desirablefeatures without various problems associated with known prior artdevices. Furthermore, the sterile fluid pathway assemblies of thepresent disclosure may filled with pharmaceutical treatments usingstandard filling equipment and systems. This advantage is enabled by thefill-finish cartridges of the present disclosure which function tomaintain the sterility of the fluid pathway assemblies and allow them tonest, mount, or otherwise be removably inserted into trays for standardfill-finish processes, as discussed is more detail below.

As discussed in more detail below, the drug delivery devices of thepresent disclosure may contain a drug, which may also be also bereferred to as a medication or a medicament. The drug may be, but is notlimited to, various biologicals (e.g., peptides, peptibodies, orantibodies), biosimilars, large-molecule drugs (e.g., a drug with amolecular weight of greater than or equal to approximately 900 Daltons),small-molecule drugs (e.g., a drug with a molecular weight of less thanor equal to approximately 900 Daltons), high viscosity drugs, lowviscosity drugs, drugs exhibiting non-Newtonian fluid characteristicssuch as shear thinning, and/or drugs exhibiting Newtonian fluidcharacteristics. The drug may be in a fluid or liquid form, although thedisclosure is not limited to a particular state (e.g., nodifferentiation is intended between a solution, a gel, or a lyophilizedproduct for example).

One perceived disadvantage of certain known drug delivery devices istheir inability to deliver highly viscous drugs such as certainbiologics in a timely manner and/or with little patient discomfort. Highviscosity drugs typically require more time for injection than lowviscosity drugs. Patients may find it difficult and/or undesirable tohold an autoinjector or a syringe against their skin for the amount oftime necessary to inject a high viscosity drug. While the injection timecan be decreased by increasing the force of the drive mechanism, a morepowerful drive mechanism increases the risk of breakage of the drugcontainer and other internal components of the device. Also, a morepowerful drive mechanism increases the possibility that the patient willexperience an impulse or mechanical shockwave that may disturb orsurprise the patient. As a result, the patient may attempt to pull thedrug delivery device away from skin, which can compromise completedosing.

Long injection times are more likely to be tolerated by patients if thedrug is administered via a wearable drug delivery device. Unlike asyringe or an autoinjector, a wearable drug delivery device does nothave to be held in place by the patient during drug delivery. Therefore,the patient can resume physical activities after the wearable drugdelivery device has been placed on the skin and initiated or otherwisenot burdened by holding the drug delivery device in place.

Certain aspects of wearable drug delivery devices, however, havediscouraged their adoption in the field of high viscosity drugs. Inorder to achieve a compact design with a low profile that does notsignificantly protrude from the patient's body, wearable drug deliverydevices oftentimes include a drug container that is offset andorthogonal to an insertion mechanism. This arrangement usually requiresa tubular conduit with one of more turns to fluidly couple the drugcontainer and the insertion mechanism. Therefore, as compared tosyringes and autoinjectors, the internal fluid flowpath of wearable drugdelivery devices tend to be relatively long and tortuous.

For drugs that behave as Newtonian fluids (i.e., fluids for which shearrate is directly proportional to flow rate), a longer flow path canresult in a slower flow rate. Thus, wearable drug delivery devices, dueto their long internal flowpaths, have the potential to exacerbate theinjection problems associated with high viscosity drugs. The force ofthe drive mechanism can be increased to compensate for the reduction inflow rate, but a more powerful drive mechanism increases the risk ofdrug container breakage and therefore is typically consideredundesirable. For at least these reasons, wearable drug delivery deviceswere viewed by some as not being particularly well suited for thedelivery of high viscosity drugs.

The inventors of the present disclosure found that various highviscosity drugs (e.g., PCSK9 specific antibodies, G-CSFs, sclerostinantibodies, and CGRP antibodies) exhibit non-Newtonian fluidcharacteristics when injected via a wearable drug delivery device. Onesuch characteristic is shear thinning, which is the ability of anon-Newtonian fluids to exhibit decreased viscosity when subjected toshear strain. Shear thinning reduces the viscosity of a fluid as it ispushed through a conduit. Accordingly, the force needed to push thefluid through a conduit is less than it would be if the fluid wasNewtonian. In the context of wearable drug delivery devices, shearshinning mitigates the clogging effect of the device's long internalflowpath. Therefore, an unexpected benefit of wearable drug deliverydevices found by the inventors of the present disclosure is that theyare well suited for delivering high viscosity drugs having non-Newtoniancharacteristics such as shear thinning. The inventors of the presentdisclosure found that shear thinning oftentimes occurs in drugs such asbiologics which have relatively large protein molecules with a molecularweight greater than or equal to approximately (e.g., ±10%) 900 daltons.Any of the wearable drug delivery devices described herein may have adrug container filled with a high viscosity drug having shear thinningcapabilities, and therefore realize the unexpected benefits of shearthinning on the operation and use of the device.

Certain non-limiting embodiments of the drug delivery device and itsrespective components will now be described with reference to theaccompanying figures.

As used herein to describe the drive mechanisms, the insertionmechanisms, fluid pathway connectors, drug delivery devices, or any ofthe relative positions of the components of the present disclosure, theterms “axial” or “axially” refer generally to a longitudinal axis “A”around which a component is preferably positioned, although notnecessarily symmetrically there-around. The term “radial” refersgenerally to a direction normal to axis A. The terms “proximal,” “rear,”“rearward,” “back,” or “backward” refer generally to an axial directionin the direction “P”. The terms “distal,” “front,” “frontward,”“depressed,” or “forward” refer generally to an axial direction in thedirection “D”. As used herein, the term “glass” should be understood toinclude other similarly non-reactive materials suitable for use in apharmaceutical grade application that would normally require glass,including but not limited to certain non-reactive polymers such ascyclic olefin copolymers (COC) and cyclic olefin polymers (COP). Theterm “plastic” may include both thermoplastic and thermosettingpolymers. Thermoplastic polymers can be re-softened to their originalcondition by heat; thermosetting polymers cannot. As used herein, theterm “plastic” refers primarily to moldable thermoplastic polymers suchas, for example, polyethylene and polypropylene, or an acrylic resin,that also typically contain other ingredients such as curatives,fillers, reinforcing agents, colorants, and/or plasticizers, etc., andthat can be formed or molded under heat and pressure. As used herein,the term “plastic” is not meant to include glass, non-reactive polymers,or elastomers that are approved for use in applications where they arein direct contact with therapeutic liquids that can interact withplastic or that can be degraded by substituents that could otherwiseenter the liquid from plastic. The term “elastomer,” “elastomeric” or“elastomeric material” refers primarily to cross-linked thermosettingrubbery polymers that are more easily deformable than plastics but thatare approved for use with pharmaceutical grade fluids and are notreadily susceptible to leaching or gas migration under ambienttemperature and pressure. As used herein, “fluid” refers primarily toliquids, but can also include suspensions of solids dispersed inliquids, and gasses dissolved in or otherwise present together withinliquids inside the fluid-containing portions of drug delivery devices.According to various aspects and embodiments described herein, referenceis made to a “biasing member”, such as in the context of one or morebiasing members for insertion or retraction of the needle, trocar,and/or cannula. It will be appreciated that the biasing member may beany member that is capable of storing and releasing energy. Non-limitingexamples include a spring, such as for example a coiled spring, acompression or extension spring, a torsional spring, and a leaf spring,a resiliently compressible or elastic band, or any other member withsimilar functions. In at least one embodiment of the present disclosure,the biasing member is a spring, preferably a compression spring. Also,as used herein, the term “drug delivery device” is intended to includeany number of devices which are capable of dispensing a fluid to apatient upon activation. Such drug delivery devices include, forexample, wearable drug delivery devices, on-body injectors, off-bodyinjectors, autoinjectors, infusion pumps, bolus injectors, and the like.Furthermore, as used herein, the term “wearable drug delivery device” isintended to include any number of devices which are capable dispensing afluid to a patient upon activation and capable of being attached to thepatient's skin or clothing. Such wearable drug delivery devices include,for example, on-body injectors and off-body injectors.

I. Drug Delivery Device

FIGS. 1A-1C show an exemplary drug delivery device 10 according to atleast one embodiment of the present disclosure. The drug delivery device10 may be utilized to administer delivery of a drug treatment into abody of a patient. As shown in FIGS. 1A-1C, the drug delivery device 10includes a housing 12. The housing 12 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug delivery device 10.For example, drug delivery device 10 includes the housing 12 whichincludes an upper housing 12A and a lower housing 12B. The drug deliverydevice 10 may further include an activation mechanism 14, a statusindicator 16, and a window 18. Window 18 may be any translucent ortransmissive surface through which the operation of the drug deliverydevice 10 may be viewed. In at least one embodiment, the window 18 maybe configured to connect and hold together the upper housing 12A and thelower housing 12B. As shown in FIG. 1B, drug delivery device 10 furtherincludes assembly platform 20, sterile fluid conduit 30, drive mechanism100 having drug container 50, insertion mechanism 200, fluid pathwayconnector 300 configured to establish a sterile fluid flow path betweenthe drug container 50 and the needle or cannula of the insertionmechanism 200, and power and control system 400. One or more of thecomponents of the drug delivery device 10 may be modular in that theymay be, for example, pre-assembled as separate components and configuredinto position onto the assembly platform 20 of the drug delivery device10 during manufacturing. In some embodiments, the assembly platform 20may be a portion of the housing 12, such as a portion of the lowerhousing 12, or alternatively, may be a separate component.

The housing 12 may contain some or all of the device components. In someembodiments, the housing 12 may provide a means of removably attachingthe drug delivery device 10 to the skin or clothing of the patient,thereby rending the drug delivery device 10 a wearable drug deliverydevice. In some embodiments, a layer of adhesive may be applied to anexterior surface of the housing 12, such as the surface through which acannula protrudes during operation, for releasably attaching the drugdelivery device 10 to a patient's skin.

The housing 12 also provides protection to the interior components ofthe drug delivery device 10 against environmental influences. In someembodiments, the housing may be configured to at least partially preventcontaminants and other harmful matter from entering the drug deliverydevice 10. For example, the housing 12 may be configured to restrict thepassage of fluids into the drug delivery device 10. As such, this mayallow the drug delivery device 10 to be worn in the shower, whileswimming, and/or other water-related activities. The housing 12 isergonomically and aesthetically designed in size, shape, and relatedfeatures to facilitate easy packaging, storage, handling, and use bypatients who may be untrained and/or physically impaired. Furthermore,the external surface of the housing 12 may be utilized to provideproduct labeling, safety instructions, and the like. Additionally, asdescribed above, housing 12 may include certain components, such asstatus indicator 16 and window 18, which may provide operation feedbackto the patient.

The container 50, or any other container described herein, may beconfigured to contain variety of different drug dose volumes, includingdrug dose volumes in a range of approximately (e.g., ±10%) 0.5-20 mL, or1-10 mL, or 2-10 mL, or 2-8 mL, or 2-6 mL, or 2-4 mL, or 0.5-2 mL, or0.5-1 mL, or 3.5 mL, or less than or equal to approximately (e.g., ±10%)3.0 mL, or less than or equal to approximately (e.g., ±10%) 2.5 mL, orless than or equal to approximately (e.g., ±10%) 2.0 mL, or less than orequal to approximately (e.g., ±10%) 1.5 mL, or less than or equal toapproximately (e.g., ±10%) 1.0 mL. The container 50 may be completely orpartially filled with the drug. The drug may be one or more of the drugsdescribed below, such as, for example, a granulocyte colony-stimulatingfactor (G-CSF), a PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9)specific antibody, a sclerostin antibody, or a calcitonin gene-relatedpeptide (CGRP) antibody.

In at least one embodiment, the drug delivery device 10 provides anactivation mechanism that is displaced by the patient to trigger a startcommand to a power and control system 400. In a preferred embodiment,the activation mechanism is a start button 14 that is located throughthe housing 12, such as through an aperture between the upper housing12A and the lower housing 12B, and which contacts a control arm 40 ofthe power and control system 400. In at least one embodiment, the startbutton 14 may be a push button, and in other embodiments, may be anon/off switch, a toggle, or any similar activation feature known in theart. The housing 12 also provides a status indicator 16 and a window 18.In other embodiments, one or more of the activation mechanism 14, thestatus indicator 16, the window 18, and combinations thereof may beprovided on the upper housing 12A or the lower housing 12B such as, forexample, on a side visible to the patient when the drug delivery device10 is placed on the body of the patient. Housing 12 is described infurther detail hereinafter with reference to other components andembodiments of the present disclosure.

The drug delivery device 10 may be configured such that, upon activationby a patient by depression of the activation mechanism, the drugdelivery device 10 is initiated to: insert a fluid pathway into thepatient; enable, connect, or open necessary connections between a drugcontainer, a fluid pathway, and a sterile fluid conduit; and force drugfluid stored in the drug container through the fluid pathway and fluidconduit for delivery into a patient. One or more optional safetymechanisms may be utilized, for example, to prevent premature activationof the drug delivery device 10. For example, an optional on-body sensor24 (shown in FIG. 1C) may be provided in one embodiment as a safetyfeature to ensure that the power and control system 400, or theactivation mechanism, cannot be engaged unless the drug delivery device10 is in contact with the body of the patient. In one such embodiment,the on-body sensor 24 is located on the bottom of lower housing 12Bwhere it may come in contact with the patient's body. Upon displacementof the on-body sensor 24, depression of the activation mechanism ispermitted. Accordingly, in at least one embodiment the on-body sensor 24is a mechanical safety mechanism, such as for example a mechanical lockout, that prevents triggering of the drug delivery device 10 by theactivation mechanism 14. In another embodiment, the on-body sensor maybe an electro-mechanical sensor such as a mechanical lock out that sendsa signal to the power and control system 400 to permit activation. Instill other embodiments, the on-body sensor can be electrically basedsuch as, for example, a conductive-, capacitive- or impedance-basedsensor which must detect tissue before permitting activation of thepower and control system 400. In at least one embodiment, such anelectrically based on-body sensor may incorporate a resistor with animpedance of approximately (e.g., ±10%) 1 MΩ. These concepts are notmutually exclusive and one or more combinations may be utilized withinthe breadth of the present disclosure to prevent, for example, prematureactivation of the drug delivery device 10. In a preferred embodiment,the drug delivery device 10 utilizes one or more mechanical on-bodysensors. Additional integrated safety mechanisms are described hereinwith reference to other components of the drug delivery device 10.

The fluid pathway connector 300 includes a sterile fluid conduit 30, apiercing member, a connection hub, and a sterile sleeve. The fluidpathway connector 300 may further include one or more flow restrictors.Upon proper activation of the drug delivery device 10, the fluid pathwayconnector 300 is enabled to connect the sterile fluid conduit 30 to thedrug container 50. Such connection may be facilitated by a piercingmember, such as a needle, penetrating a pierceable seal of the drugcontainer 50. The sterility of this connection may be maintained byperforming the connection within a flexible sterile sleeve. Uponsubstantially simultaneous activation of the insertion mechanism, thefluid pathway between drug container and insertion mechanism is completeto permit drug delivery into the target tissue.

In at least one embodiment of the present disclosure, the piercingmember of the fluid pathway connector is caused to penetrate thepierceable seal of the drug container of the drive mechanism by directaction of the user, such as by depression of the activation mechanism bythe user. For example, the activation mechanism itself may bear on thefluid pathway connector such that displacement of the activationmechanism from its original position also causes displacement of thefluid pathway connector. In a preferred embodiment, this connection isenabled by the user depressing the activation mechanism and, thereby,driving the piercing member through the pierceable seal, because thisprevents fluid flow from the drug container until desired by the user.In such an embodiment, a compressible sterile sleeve may be fixedlyattached between the cap of the drug container and the connection hub ofthe fluid pathway connector. The piercing member may reside within thesterile sleeve until a connection between the fluid pathway connectorand the drug container is desired. The sterile sleeve may be sterilizedto ensure the sterility of the piercing member and the fluid pathwayprior to activation.

Alternatively, or additionally, the sterility of the flow path may bepreserved by one or more membranes or foils defining one or more sterilechambers of the fluid pathway connector. The membranes or foils may bepierced at the time of use of the drug pump by the piercing member or,alternatively, by an introducer member. In such an embodiment, thepiercing member may be at least partially disposed within a lumen of theintroducer member to prevent the piercing member from coming in contactwith foreign substances.

The drug pump is capable of delivering a range of drugs with differentviscosities and volumes. The drug pump is capable of delivering a drugat a controlled flow rate (speed) and/or of a specified volume. In oneembodiment, the drug delivery process is controlled by one or more flowrestrictors within the fluid pathway connector and/or the sterile fluidconduit. In other embodiments, other flow rates may be provided byvarying the geometry of the fluid flow path or delivery conduit, varyingthe speed at which a component of the drive mechanism advances into thedrug container to dispense the drug therein, or combinations thereof.Still further details about the fluid pathway connector 300 and thesterile fluid conduit 30 are provided hereinafter in later sections inreference to multiple embodiments.

Another embodiment of a drug delivery device 6010 is shown in FIGS.2A-2B. The drug delivery device 6010 includes many of the same elementsas the drug delivery device 10. Elements of the drug delivery device6010 which are similar to, or the same as, the drug delivery device 10are designated by the same reference numeral, incremented by 6010. Adescription of many of these elements is abbreviated or even eliminatedin the interest of brevity. The drug delivery device 6010 may include acontainer 6050 filled with a volume of a fluid(s) for delivery to apatient. The fluid(s) may include one or more of the drugs describedbelow, such as, for example, a granulocyte colony-stimulating factor(G-CSF), a PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9)specific antibody, a sclerostin antibody, or a calcitonin gene-relatedpeptide (CGRP) antibody. In drug delivery device 6010, one or more of aninsertion mechanism 6200, fluid pathway connector 6300, and a drivemechanism 6100 are controlled by motion of a motor 6207, solenoid orother electrical actuator, as well as the rotation of one or more gears6209. Additionally, or alternatively, an escapement mechanism may beused to control the rate of rotation of the one or more gears 6209. Oneof the gears 6209 may be engaged with teeth 6208 of an insertionmechanism housing 6202. As such, the rotation of the one or more gears209 of the gear train may control the rotation of the insertionmechanism housing 6202 and, thereby, the insertion of the needle ortrocar into the skin of the patient. The operation of variousembodiments of the insertion mechanism 6200 are described in more detailbelow.

II. Power and Control System

The power and control system 400 includes a power source, which providesthe energy for various electrical components within the drug deliverydevice 10, one or more feedback mechanisms, a microcontroller, a circuitboard, one or more conductive pads, and one or more interconnects. Othercomponents commonly used in such electrical systems may also beincluded, as would be appreciated by one having ordinary skill in theart. The one or more feedback mechanisms may include, for example,audible alarms such as piezo alarms and/or light indicators such aslight emitting diodes (LEDs). The microcontroller may be, for example, amicroprocessor. The power and control system 400 controls several deviceinteractions with the patient and interfaces with the drive mechanism100. In one embodiment, the power and control system 400 interfaceseither directly or indirectly with the on-body sensor 24 to identifywhen the device is in contact with patient and/or the activationmechanism 14 to identify when the drug delivery device 10 has beenactivated. The power and control system 400 may also interface with thestatus indicator 16 of the housing 12, which may be a transmissive ortranslucent material which permits light transfer, to provide visualfeedback to the patient. The power and control system 400 interfaceswith the drive mechanism 100 through one or more interconnects to relaystatus indication, such as activation, drug delivery, and end-of-dose,to the patient. Such status indication may be presented to the patientvia auditory tones, such as through the audible alarms, and/or viavisual indicators, such as through the LEDs. In a preferred embodiment,the control interfaces between the power and control system and theother components of the drug delivery device 10 are not engaged orconnected until activation by the patient. This is a desirable safetyfeature that prevents accidental operation of the drug delivery device10 and may additionally maintain the energy contained in the powersource during storage, transportation, and the like.

The power and control system 400 may be configured to provide a numberof different status indicators to the patient. For example, the powerand control system 400 may be configured such that after the on-bodysensor and/or trigger mechanism have been pressed, the power and controlsystem 400 provides a ready-to-start status signal via the statusindicator 16 if device start-up checks provide no errors. Afterproviding the ready-to-start status signal and, in an embodiment withthe optional on-body sensor, if the on-body sensor remains in contactwith the body of the patient, the power and control system 400 willpower the drive mechanism 100 to begin delivery of the drug treatmentthrough the fluid pathway connector 300 and sterile fluid conduit 30 tothe needle or cannula of the insertion mechanism 200. In a preferredembodiment of the present disclosure, the insertion mechanism 200 andthe fluid pathway connector 300 may be caused to activate directly bypatient operation of the activation mechanism 14. During the drugdelivery process, the power and control system 400 is configured toprovide a dispensing status signal via the status indicator 16. Afterthe drug has been administered into the body of the patient and afterthe end of any additional dwell time, to ensure that substantially theentire dose has been delivered to the patient, the power and controlsystem 400 may provide an okay-to-remove status signal via the statusindicator 16. This may be independently verified by the patient byviewing the drive mechanism 100 and drug dose delivery through thewindow 18 of the housing 12. Additionally, the power and control system400 may be configured to provide one or more alert signals via thestatus indicator 16, such as for example alerts indicative of fault oroperation failure situations.

Additionally, the power and control system 400 may be configured toidentify removal of the drug delivery device from its packaging. Thepower and control system 400 may be mechanically, electronically, orelectro-mechanically connected to the packaging such that removal of thedrug delivery device from the packaging may activate or power-on thepower and control system for use, or simply enable the power and controlsystem to be powered-on by the patient. In such an embodiment, withoutremoval of the drug delivery device from the packaging the drug deliverydevice cannot be activated. This provides an additional safety mechanismof the drug delivery device 10 and for the patient. In at least oneembodiment, the drug delivery device 10 or the power and control systemmay be electronically or electro-mechanically connected to thepackaging, for example, such as by one or more interacting sensors froma range of: Hall effect sensors; giant magneto resistance (GMR) ormagnetic field sensors; optical sensors; capacitive or capacitancechange sensors; ultrasonic sensors; and linear travel, LVDT, linearresistive, or radiometric linear resistive sensors; and combinationsthereof, which are capable of coordinating to transmit a signal betweencomponents to identify the location there-between. Additionally oralternatively, the drug delivery device or the power and control systemmay be mechanically connected to the packaging, such as by a pin andslot relationship which activates the system when the pin is removed(i.e., once the drug delivery device is removed from the packaging).

In a preferred embodiment of the present disclosure, once the power andcontrol system 400 has been activated, a multi-function drive mechanism(e.g., drive mechanism 100) is initiated to actuate the insertionmechanism 200 and the fluid pathway connector 300, while also permittingthe drug fluid to be forced from the drug container 50. During the drugdelivery process, the power and control system 400 is configured toprovide a dispensing status signal via a status indicator (e.g., statusindicator 16). After the drug has been administered into the body of thepatient and after the end of any additional dwell time, to ensure thatsubstantially the entire dose has been delivered to the patient, thepower and control system 400 may provide an okay-to-remove status signalvia the status indicator. This may be independently verified by thepatient by viewing the drive mechanism and drug dose delivery throughthe window 18 formed in the housing 12. Additionally, the power andcontrol system 400 may be configured to provide one or more alertsignals via the status indicator, such as for example alerts indicativeof fault or operation failure situations.

The power and control system 400 may additionally be configured toaccept various inputs from the patient to dynamically control the drivemechanisms 100 to meet a desired drug delivery rate or profile. Forexample, the power and control system 400 may receive inputs, such asfrom partial or full activation, depression, and/or release of theactivation mechanism, to set, initiate, stop, or otherwise adjust thecontrol of the drive mechanism 100 via the power and control system 400to meet the desired drug delivery rate or profile. Similarly, the powerand control system 400 may be configured to receive such inputs toadjust the drug dose volume; to prime the drive mechanism, fluid pathwayconnector, and fluid conduit; and/or to start, stop, or pause operationof the drive mechanism 100. Such inputs may be received by the patientdirectly acting on the drug delivery device 10, such as by use of theactivation mechanism 14 or a different control interface, or the powerand control system 400 may be configured to receive such inputs from aremote control device. Additionally or alternatively, such inputs may bepre-programmed.

Other power and control system configurations may be utilized with thedrug delivery device of the present disclosure. For example, certainactivation delays may be utilized during drug delivery. As mentionedabove, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to thepatient. Similarly, activation of the drug delivery device 10 mayrequire a delayed depression (i.e., pushing) of the activation mechanism14 of the drug delivery device 10. Additionally, the system may includea feature which permits the patient to respond to the end-of-dosesignals and to deactivate or power-down the drug delivery device 10.Such a feature may similarly require a delayed depression of theactivation mechanism, to prevent accidental deactivation of the device.Such features provide desirable safety integration and ease-of-useparameters to the drug delivery device 10. An additional safety featuremay be integrated into the activation mechanism to prevent partialdepression and, therefore, partial activation of the drug deliverydevice. For example, the activation mechanism and/or power and controlsystem may be configured such that the device is either completely offor completely on, to prevent partial activation. Such features aredescribed in further detail hereinafter with regard to other aspects ofthe drug delivery device 10.

The foregoing description of the power and control system 400 applies tothe power and control system 6400 of the drug delivery device 6010,where appropriate.

III. Fluid Pathway Connector

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, may be configured to incorporate the embodiments of the fluidpathway connector described below in connection with FIGS. 3A-32B. Theembodiments of the fluid pathway connector described below in connectionwith FIGS. 3A-32B may be used to replace, in its entirety or partially,the above-described fluid pathway connector 300 or 6300, or any otherfluid pathway connector described herein, where appropriate.

The present disclosure provides container connections which maintain thesterility and/or aseptic condition of the fluid pathway, and drugdelivery pumps which incorporate such sterile fluid pathway connectorassemblies to drug containers. Such devices are safe and easy to use,and are aesthetically and ergonomically appealing for self-administeringpatients. The fluid pathway connector may be initiated directly by theuser, or may be activated by another mechanism of the device (asdescribed herein) after some initial user step. The devices describedherein incorporate features which make activation, operation, andlock-out of the device simple for even untrained users. The noveldevices of the present disclosure provide these desirable featureswithout problems associated with known prior art devices. Certainnon-limiting embodiments of the novel drug delivery pumps, fluid pathwayconnector assemblies, and their respective components are describedfurther herein with reference to the accompanying figures.

Conventional drug delivery devices often require filling at time-of-usebecause the terminal sterilization of the device cannot be completedwith the pharmaceutical drug within the drug container. Variouspharmaceutical drugs cannot withstand the temperatures, pressures, andother conditions necessary for sterilization of the device afterassembly. In other words, because existing manufacturing processesrequire sterilization of the entire device, the drug cannot be“pre-filled” into the device prior to sterilization. This adds a complexstep after final assembly of the device, which often requires costlyadditional equipment, handling of separate drug containers, and/ortraining of the patient to perform the filling step themselves prior toinjection. Instead, the embodiments of the present disclosure enable themanufacture, assembly, and use of pre-filled drug delivery devices whichmaintain the sterility and/or aseptic condition of the fluid pathwayassembly through the various manufacturing steps.

Additionally, because the drug delivery devices according to the presentdisclosure do not need to be terminally sterilized, the components ofthe devices may be constructed of other, often less expensive, materialswhich would not normally withstand the sterilization environment. Forexample, less expensive plastics may be utilized for certain devicecomponents because they do not need to be sterilized after assembly.Furthermore, the embodiments of the present disclosure permit devicearchitecture and/or component integration in ways which are not suitablefor devices that require terminal sterilization. For example, whensterilization of the entire device is necessary, the device architectureoften requires adequate spacing of components to permit thesterilization gas or material to effectively reach the target surfaces.Removing the need for terminal sterilization permits reduction orelimination of those spaces and allows for device architectures thatoffer smaller overall dimensions, human factors benefits, and/orindustrial design options that are not available for devices thatrequire terminal sterilization.

In other words, the embodiments of the present disclosure may allow themanufacturer to sterilize only the components which will be in contactwith the drug fluid and/or which are necessary to maintain sterileand/or aseptic fluid pathways. These embodiments may also allow thepharmaceutical filler to maintain the sterility and/or aseptic conditionof these components during the filling and finishing steps associatedwith the assembly of the drug delivery devices. Similarly, drug deliverydevices which incorporate the fluid pathway connector assemblies of thepresent disclosure may have smaller or more efficient geometries as thedevice does not have to be configured for sterilization after assembly.

Additionally, the embodiments of the present disclosure allow for theutilization of standard fill-finish processes to fill the drugcontainer. This greatly simplifies the manufacturing processes used tobuild drug delivery devices. Standard fill-finish processes utilizetrays which hold multiple drug containers, such as syringes. Theembodiments of the present disclosure enable a drug delivery devicemanufacturer, pharmaceutical company, or contract drug filler to fillthe drug containers for infusion or injection pumps using the samestandard fill-finish processes. These drug containers can be filledaseptically, as is common industry practice, in a cost-efficient manner.After mounting of the fluid pathway connector assembly the combinedassembly can then be mated into a drug delivery device without requiringthe remainder of the device components to be sterilized. Accordingly,embodiments of the present disclosure may provide novel components whichenable the fluid pathway assemblies to be sterilized, assembled, filled,and incorporated into drug delivery devices in a cost-efficient andstreamlined process.

In the processes of filling drug containers and other drug deliverydevices, it is sometimes necessary to connect two or more sterilecomponents or subassemblies. For example, wearable injectors or drugdelivery devices may include a drug container which may be filled with afluid drug using standard pharmaceutical fill-finish processes. Afterfilling of the drug container, it may be necessary to connect the drugcontainer to one or more additional components or subassemblies suchthat a fluid communication may be established between the drug containerand these components. Maintaining the fluid path in an aseptic conditionis critical, preventing the introduction of harmful microbes orparticulates to the drug and/or fluid pathway. The connection of two ormore aseptic components or subassemblies is typically performed in anaseptic environment, such as a clean room, thereby ensuring that noharmful microbes or particulates are introduced to the assembly. This,however, may lead to increased cost to manufacture the drug deliverydevices.

The present disclosure provides fluid pathway connector assemblies withintegrated safety features and drug delivery pumps which incorporatesuch fluid pathway connector assemblies. Such devices are safe and easyto use, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. The novel devices of the presentdisclosure provide these desirable features without any of the problemsassociated with known prior art devices. Certain non-limitingembodiments of the novel drug delivery device, fluid pathway connectorassemblies, and their respective components are described further hereinwith reference to the accompanying figures. The devices described hereinmay be configured for delivery of controlled substances and may furtherinclude features that prevent so-called “run-away” delivery ofmedicament. When delivering controlled substances, this may be animportant safety feature to protect the patient. For example, somemedicaments can be dangerous, and potentially even deadly, whenadministered in too large a quantity and/or at too rapid of a rate. Byproviding such automatic safety stop mechanisms, the safety of thepatient may be ensured.

The present disclosure provides devices and methods for establishingaseptic connections between two or more components or subassemblies. Thedevices may be used in medical devices such as drug delivery pumps. Insome embodiments, a connection is made between a drug container and afluid pathway connector assembly. The fluid pathway connector assemblymay include a connection hub, a piercing member, and a piercing memberretainer. The mechanism may further include a first film or sealcovering an aperture, thereby maintaining the aseptic condition of acavity adjacent the aperture. The drug container may hold a fluid drugand include a pierceable seal. A second film may cover an aperture ofone or more components of the drug container and the seal, and therebymaintain the aseptic condition of the pierceable seal. The piercingmember may be caused to pierce the first and second film and thepierceable seal to open a fluid pathway for delivery of the fluid drugto a patient.

In a first embodiment, the present disclosure provides a fluid pathwayconnector. The fluid pathway connector assembly includes: a connectionhub, a piercing member, a piercing member retainer, and a drug containerhaving a cap, a pierceable seal, and a barrel, wherein the piercingmember is at least partially disposed in a sterile cavity defined by theconnection hub. The drug container may contain a drug fluid for deliverythrough the fluid pathway connector assembly to the target. Thepierceable seal includes a seal barrier that may be penetrated by thepiercing member. The fluid pathway connector assembly may furtherinclude a first film which is fixedly attached over an aperture over anaperture of the connection hub and prevents foreign substances such asmicrobes from entering the sterile cavity formed by the connection hub.The drug container may further include a second film fixedly connectedover a cavity formed by the pierceable seal and the second film toprevent foreign substances such as microbes from entering the cavity.The first and second films may be pierced by the piercing member. Thefluid pathway connector may be initiated directly by the user, or may beactivated by another mechanism of the device (as described herein) aftersome initial user step.

In another embodiment, the present disclosure provides a drug deliverypump with integrated sterility maintenance features having a housing andan assembly platform, upon which an activation mechanism, a fluidpathway connector assembly, a power and control system, and a drivemechanism having a drug container may be mounted, said fluid pathwayconnector assembly including a connection hub, a piercing member, apiercing member retainer, and a drug container having a cap, apierceable seal, and a barrel, wherein the piercing member is at leastpartially disposed in a sterile cavity defined by the connection hub.The drug container may contain a drug fluid for delivery through thefluid pathway connector assembly to the target. The pierceable sealincludes a seal barrier that may be penetrated by the piercing member.The fluid pathway connector assembly may further include a first filmwhich is fixedly attached over an aperture over an aperture of theconnection hub and prevents foreign substances such as microbes fromentering the sterile cavity formed by the connection hub. The fluidpathway connector assembly may further include a second film fixedlyconnected over a cavity formed by the pierceable seal and preventsforeign substances such as microbes from entering the cavity. The firstand second films may be pierced by the piercing member.

The devices described herein may further include features which preventthe delivery of an excess volume of medicament or delivery at too rapidof a rate, e.g., to prevent a run-away condition of uncontrolled orundesired delivery of the medicament. By providing such automatic safetymechanisms, the safety of the patient may be ensured. Some medicaments,such as insulin or other treatments for diabetes, can be dangerous, andpotentially even deadly, if they are not delivered according toprescribed parameters. The safety features described below may ensurethat delivery of the medicament is terminated if delivery deviates fromthe specified parameters.

In a further embodiment of the present disclosure, the fluid pathwayconnector assembly may include one or more biasing members. In one suchembodiment, a biasing member may be included to bias the fluid pathwayconnector assembly to connect, i.e., to open the fluid pathway betweenthe drug container and the fluid conduit which enables drug flow to theneedle insertion mechanism and into the target. In such a configuration,the fluid pathway connector assembly is biased to facilitate theconnection upon, for example, movement of a pin or blocking aspect. Inat least one embodiment, the biasing member(s) may be internal to thefluid pathway connector assembly and/or external to the fluid pathwayconnector assembly to facilitate the connection once triggered.Additionally or alternatively, one or more biasing members may beincluded to disconnect the fluid pathway connector assembly. This mayprovide a desirable safety feature, to disconnect the fluid pathway uponsignaling of an error condition either automatically by the drugdelivery pump or upon action by the user. Once the fluid pathwayconnector assembly is disconnected, flow of drug fluid is restricted orblocked between the drug container and the fluid conduit to limit orprevent fluid flow to the needle insertion mechanism and into thetarget.

According to an aspect of the disclosure, there is provided a fluidpathway connector assembly for use with a drug container in a drugdelivery pump. The drug container includes a barrel, a cap and apierceable seal. The fluid pathway connector assembly includes anunactuated configuration, an actuated configuration, and a deliveryconfiguration. The fluid pathway connector assembly includes aconnection hub including an aperture, a first film, an introducermember, a piercing member, and a piercing member retainer. The firstfilm is sealed along the aperture. The connection hub includes a sterilecavity sealed by the first film. The introducer member is at leastpartially disposed within the sterile cavity in the unactuatedconfiguration. The piercing member is configured to telescope from theintroducer member. The piercing member includes a piercing tip at leastpartially disposed within the introducer member in the unactuatedconfiguration. The piercing member retainer is connected to the piercingmember. The introducer member is configured to move relative to theconnection hub from the unactuated configuration to the actuatedconfiguration in which the introducer member pierces the first film. Thepiercing member is configured to telescope from the introducer member tomove from the unactuated configuration to the delivery configuration inwhich the piercing tip is not disposed within the introducer member. Thepiercing member is adapted to pierce the pierceable seal in the deliveryconfiguration, the piercing member providing a fluid pathway through thepiercing member connection hub in the delivery configuration. In atleast one embodiment, there is provided a combination of the fluidpathway connector assembly and the drug container. In at least oneembodiment, there is provided a drug delivery pump including a housing,an activation mechanism, the fluid pathway connector assembly, and adrug container.

In at least one embodiment, the fluid pathway connector assembly isconfigured to move the piercing member from the delivery configurationto a retracted configuration wherein the piercing member is disengagedfrom the pierceable seal in response to a termination mechanism.

Described below are embodiments of fluid pathway connector assemblies toallow connections to be made between two or more components orsubassemblies of the drug delivery devices disclosed herein in a septicenvironment while maintaining the aspect condition of the fluid flowpath. As will be seen, the fluid pathway connector assemblies may bearranged in any orientation. For example, as illustrated in FIGS. 3A-11,the piercing member may be axially aligned with the drug container. Inother embodiments, as shown in FIGS. 23-30, the fluid pathway connectorassembly may be arranged such that the piercing member of the fluidpathway connector assembly is oriented at an angle with respect to thedrug container. In an alternative embodiment, the piercing member may bearranged in an arcuate manner. An exemplary embodiment of such anarrangement is shown in FIGS. 12A-22. The orientation of the fluidpathway connector assembly may be chosen based on the desired overallsize and shape of drug delivery device 10 and the available space withinthe drug delivery device 10.

FIGS. 3A-11 show one embodiment of such a fluid pathway connector. Asseen in FIGS. 3A-3B, the fluid pathway connector 300 may be connected tothe drug container 50. FIG. 3A shows these components prior toconnection and FIG. 3B shows the components after connection. As will bedescribed herein, fluid pathway connector 300 may be mounted to drugcontainer 50 without compromising the aseptic condition of the fluidflow path. Fluid pathway connector 300 includes introducer member 320,piercing member 316, introducer member retainer 330, piercing memberretainer 314, connection hub 312, plate 334, biasing member 336, sterileboot 340, and first film 318. FIGS. 4A-4B show exploded views of thefluid pathway connector 300. As used herein, “piercing member” may referto any container access needle having at least one pointed end and ahollow interior configured to establish fluid communication with thedrug container 50.

According to one aspect of the disclosure (see FIGS. 5A and 5B), theconnection hub 312 includes a cavity 312A. Sterile boot 340 may furtherdefine the cavity 312A as aseptic. In one embodiment, sterile boot 340is fixedly connected at a first end to connection hub 312 and at asecond end to introducer member retainer 330. Sterile boot 340 may beconstructed from a flexible material, such as an elastomer, therebyallowing the sterile boot to deform to maintain engagement with bothconnection hub 312 and introducer member retainer 330 during operation.A first film 318 is disposed covering an aperture 312B of connection hub312 to prevent microbes and other contaminants from entering cavity 312Athrough aperture 312B. In this way, the area contained or bounded by thesterile boot 340, the connection hub 312, and the first film 318 definescavity 312A and maintains the aseptic condition of the cavity 312A.

In an unmounted configuration, such as illustrated in FIG. 3B, and in aninitial, unactuated configuration, as shown in FIGS. 5A-5B, at least aportion of introducer member 320 is disposed within aseptic cavity 312A.At least a piercing tip of the piercing member 316 is partially retainedwithin lumen 320A of introducer member 320, the piercing member 316being disposed to telescope within the introducer member 320. Thepiercing member 316 is also at least partially disposed in piercingmember retainer 314. In this way, introducer member 320 and piercingmember 316 are likewise maintained in an aseptic condition within cavity312A.

Piercing member 316 is engaged with piercing member retainer 314 suchthat translation of piercing member retainer 314 is transferred topiercing member 316 such that they maintain a substantially fixedspatial relationship throughout operation. Piercing member 316 may beengaged with piercing member retainer 314 using any method known to oneskilled in the art, such as bonding, press-fit, staking, etc. Thepiercing member 316 may be, for example, a hollow needle.

Introducer member 320 is at least partially retained by introducermember retainer 330 and is engaged with the introducer member retainer330 such that translation of introducer member retainer 330 istransferred to introducer member 320 such that they maintain asubstantially fixed spatial relationship throughout operation.Introducer member 320 may be engaged with introducer member retainer 330using any method known to one skilled in the art, such as bonding,press-fit, staking, or any other appropriate method.

Piercing member retainer 314 and introducer member retainer 330 areengaged with connection hub 312 and may be configured for translationwith respect to the connection hub in a direction parallel to the longaxis of piercing member 316 (axis “A” shown in FIG. 5B). Connection hub312, piercing member retainer 314, and introducer member retainer 330may include one or more features to maintain orientation and positionwith respect to one another as will be described in more detail below.

The fluid pathway connector 300 may further be provided with aninsertion driver disposed to advance one or both of the piercing member316 and the introducer member 320 toward the drug container 50. In thisembodiment, at least one biasing member 336 is provided to advance oneor both of the piercing member 316 and the introducer member 320 towardthe drug container 50. Biasing member 336 is initially in a compressedor energized condition and is restrained from decompressing orde-energizing. A first end of biasing member 336 is in contact withplate 334, which is axially stationary, and a second end of biasingmember 336 is in contact with piercing member retainer 314. In oneembodiment, biasing member 336 is in contact with shoulder 314D ofpiercing member retainer 314. Motion of plate 334 is restrained byengagement with snaps 312C of connection hub 312 (see FIG. 9) which areinserted through passages 334A of plate 334 (see FIG. 9) duringassembly. In an initial configuration, shaft 314A of piercing memberretainer 314 (see FIG. 10) passes through central bore 334B of plate 334and is engaged by interlock 338 (see FIGS. 3A, 3B, 5A, 5B). Interlock338 is located on the distal side of plate 334 and engages one or morelobes 314B on shaft 314A to prevent translation of piercing memberretainer 314 with respect to plate 334. In this way, decompression orde-energizing of biasing member 336 is restrained. As will be describedfurther herein, transformation of interlock 338, to a configuration inwhich it does not restrain translation of piercing member retainer 314,allows decompression of biasing member 336 and connection of the fluidpathway to drug container 50.

The drug container 50 may include a crimp cap 324 that maintains aconnection between a pierceable seal 326 and a barrel 58. The pierceableseal maintains the fluid drug within the barrel and prevents microbesand other substances from entering the drug chamber. A recess 328 (bestseen in FIG. 5B) is formed by the geometry of the pierceable seal 326. Asecond film 322 is affixed to the drug container such that it enclosesrecess 328, thereby maintaining recess 328 in an aseptic condition.

The first and second films may be constructed of any material capable ofproviding the barrier properties required to maintain the asepticcondition of the associated surfaces. In a preferred embodiment, thefilms are constructed from a foil material. Alternatively, the films maybe any type of sterilizable membrane, film, or foil. Additionally, thefilm may be removable and/or pierceable as well as breathable and/orpermeable.

A surface treatment may be applied to the exterior surfaces of bothfirst film 318 and second film 322 prior to joining the fluid pathwayconnector and the drug container. The surface treatment may containantimicrobial, antibacterial, or antiviral compounds to limit or reducethe number of such substances on the surface of the seals.

Connection hub 312 may include a barrel-engaging aspect 312D.Barrel-engaging aspect 312D may include one or more flex arms 312Econfigured to engage crimp cap 324 and/or neck 58A of barrel 58. Duringconnection, flex arms 312E may engage crimp cap 324 or another portionof the drug container, thereby limiting axial translation of the fluidpathway connector with respect to the drug container. In this position,first film 318 and second film 322 are in contact with, or in closeproximity to, one another. In one embodiment, first film 318 and secondfilm 322 include an adhesive such that the films are bonded to oneanother during assembly.

FIGS. 5A-5B show a cross-sectional side view of the connection hub 312and drug container 50 in a mounted, unactuated configuration, that is,after they have been joined. In this configuration, introducer member320 is at least partially disposed within cavity 312A and engagement ofinterlock 338 with piercing member retainer 314 retains biasing member336 in a compressed or energized state. First film 318 and second film322 are intact, thereby maintaining the aseptic condition of cavity 312Aand pierceable seal 326, respectively.

An actuated configuration is illustrated in FIGS. 6A-6B. In oneembodiment, activation may displace or transform interlock 338 such thatit no longer restricts translation of piercing member retainer 314. Uponactivation, the piercing member retainer 314 and introducer memberretainer 330 may be translated axially with respect to the connectionhub and drug container 50. The translation may be caused bydecompression or de-energizing of biasing member 336. In one embodiment,biasing member 336 is a compression spring. Because piercing memberretainer 314 is in contact with introducer member retainer 330, aspiercing member retainer 314 translates, introducer member retainer 330translates together with piercing member retainer 314. For example,proximal face 314C of piercing member retainer 314 (see FIG. 10) maycontact projections 330A of introducer member retainer 330 (see FIG.11). Proximal face 314C may include a chamfered or radiused portionwhich contacts projections 330A. The contacting faces of piercing memberretainer 314 and introducer member retainer 330 may be configured suchthat piercing member retainer 314 applies a radially inwardly directedforce to projections 330A and, thereby, extensions 330D, in addition toan axial force. However, initially, fingers 330C of extensions 330D areprevented from inward displacement by contact with ribs 312G ofconnection hub 312 (see FIGS. 4A, 4B, 6B). Hence, introducer memberretainer 330 translates along with piercing member retainer 314.Translation of the piercing member retainer 314 causes piercing member316 to translate and translation of the introducer member retainer 330causes translation of the introducer member 320. This translation causesthe introducer member 320 to pierce first film 318 and second film 322,as shown in FIGS. 6A-6B. It will be appreciated that, because thepiercing member 316 is disposed within introducer member 320, it doesnot contact the first 318 and second 322 films; hence, any contaminantspresent on the surface of the films do not come in contact with thepiercing member 316.

After the introducer member 320 pierces first film 318 and second film322, translation of introducer member retainer 330 is restricted suchthat its translation is terminated with the tip of the introducer memberdisposed in recess 328 (i.e., the introducer member does not passthrough pierceable seal 326). Translation of introducer member retainer330 may, for example, be restricted by contact of a portion of theproximal face 330B with flange 312F of connection hub 312. It is notnecessary that the entire proximal face 330B of introducer memberretainer 330 contact flange 312F. For example, fingers 330C may contactflange 312F. In this position, fingers 330C are no longer in contactwith ribs 312G of connection hub 312. Because of this, extensions 330Dare able to flex radially inward. As a result, continued decompressionof biasing member 336 and translation of piercing member retainer 314causes the extensions 330D to move inward and piercing member retainer314 is able to pass over introducer member retainer 330.

Turning now to FIGS. 7A-7B, there is illustrated a deliveryconfiguration of the fluid pathway connector 300. Continueddecompression of biasing member 336 may cause the piercing memberretainer 314 to be further displaced, leading to the piercing ofpierceable seal 326 by piercing member 316. Hence, with furthertranslation of introducer member retainer 330 prevented by contact withconnection hub 312, continued decompression of biasing member 336 causespiercing member retainer 314 to translate in a proximal directionrelative to introducer member retainer 330. After piercing of thepierceable seal, a fluid path is established from the drug container andthrough the piercing member 316. Those of skill in the art willappreciate that the piercing member 316 may also be in fluidcommunication with a conduit 30 (as in FIG. 31), the conduit beingconfigured to carry the fluid contents to a delivery mechanism, such asan insertion mechanism, for delivery to a patient.

In an alternative embodiment, piercing of the first and second filmsoccurs at the time of assembly. In such an embodiment, piercing of thepierceable seal at or near the time-of-use may be initiated byinteraction with an activation mechanism.

In at least one embodiment, the first and second films are pierced bythe introducer member at a first time, for example time of assembly, andthe piercing member pierces the pierceable seal at a later time, forexample upon activation. In such an embodiment, the end of the piercingmember may remain disposed within recess 328 until time-of-use. Thepierceable seal may be configured such that, in response to hydraulicand/or pneumatic pressure within the drug chamber, pierceable seal 326deforms or is displaced and is caused to come into contact with thepiercing member. This deformation of the pierceable seal 326 leads tothe piercing of the seal by the piercing member 316. In such anembodiment, introducer member 320 may be retracted after piercing thefirst and second films.

Although the embodiment shown in FIGS. 3A-11 is configured such thatpiercing member 316 is substantially axially aligned with drug container50, one skilled in the art would recognize that this orientation can beconfigured in any orientation. For example, the axis of piercing member316 may be oriented orthogonal to the central axis of the drug container50. Alternatively, the axes may be oriented at any angle betweenparallel and orthogonal. Selection of this angle or orientation may bechosen based on the space requirements of drug delivery device 10.

In another embodiment, shown in FIGS. 12A-22, the introducer member andpiercing member are arranged in an arcuate manner. The arcuateconfiguration of the fluid pathway connector may allow the footprint ofthe fluid pathway connector to be reduced, allowing for a smalleroverall size of drug delivery device 10. Fluid pathway connector 1300includes introducer member 1320, piercing member 1316, introducer memberretainer 1330, piercing member retainer 1314, connection hub 1312, shaft1342, and first film 1318. As described above, connection hub 1312 maybe configured to engage drug container 1050, for example, by engagingcrimp cap 1324 and/or neck 1058A of drug container 1050.

Introducer member 1320 may be either directly or indirectly coupled tointroducer member retainer 1330. For example, in the embodiment shown,introducer member 1320 is fixedly connected to first sleeve 1344. Inturn, first sleeve 1344 is engaged with second sleeve 1346. Finally,second sleeve 1346 is engaged with introducer member retainer 1330, forexample by the keyed engagement shown. First sleeve 1344 and secondsleeve 1346 may further retain septum 1348, through which piercingmember 1316 may pass.

Similarly, piercing member 1316 may be directly or indirectly coupled topiercing member retainer 1314. In the embodiment shown, piercing member1316 is engaged with keeper 1350. Keeper 1350 is engaged with piercingmember retainer 1314 by, for example, the keyed arrangement shown.

In an initial, unactuated configuration, shown in FIGS. 13A-13B,introducer member 1320 is initially at least partially disposed incavity 1312A. Piercing member 1316 is at least partially disposed withinthe lumen 1320A of introducer member 1320. Cavity 1312A is maintained inan aseptic condition by first film 1318. The aseptic condition of cavity1312A may be further maintained by cap 1354 and ring seal 1352. Ringseal 1352 is held in sealing engagement with connection hub 1312 and/orintroducer member 1320 by cap 1354. Although ring seal 1352 is shownhere with a circular cross-section, the ring seal may take on any shapeknown to one skilled in the art. Alternatively, for example, the asepticcondition may be maintained by a septum.

Upon activation, introducer member retainer 1330 and piercing memberretainer 1314 are caused to rotate about shaft 1342. It will beappreciated that shaft 1342 may be integrally formed with connection hub1312, as shown in FIG. 20, may be a feature of housing 12, or may be apin or other component engaged with connection hub 1312 or housing 12.While the latter two of these embodiments are not specificallyillustrated, they will be readily understood by those of skill in theart. An insertion driver may be provided to advance one or both of thepiercing member 1316 and the introducer member 1320 toward the drugcontainer 1050. For example, the rotation about the axis of the shaftmay be caused by de-energizing of a biasing member, such as a torsionspring. Alternatively, the rotation may be caused by a driving member ofdrug delivery device 10. For example, needle insertion mechanism 200 mayinclude a driving member that, upon activation, contacts an aspect ofpiercing member retainer 1314 and causes rotation of piercing memberretainer 1314 and introducer member retainer 1330. In anotherembodiment, the biasing member of the needle insertion mechanism bearsagainst the piercing member retainer 1314 and causes rotation thereof.

Piercing member retainer 1314 and introducer member retainer 1330 mayinitially rotate as a unit. Referring to FIGS. 16B and 22, introducermember retainer 1330 may initially be disposed between projection 1314Eand tooth 1314F, both features of piercing member retainer 1314. Theretainers move in conjunction to the actuated configuration shown inFIGS. 14A-14B. In this position, the introducer member 1320 has piercedthe first film 1318 and second film 1322, but has not pierced pierceableseal 1326. At or near to this position, flex arm 1314G of piercingmember retainer 1314 contacts connection hub 1312 and/or cap 1354.Hence, continued rotation of piercing member retainer 1314 causes flexarm 1314G to be displaced downward. As a result, contact of projection1314E with introducer member retainer 1330 no longer causes rotation ofintroducer member retainer 1330. Thus, further rotation of piercingmember retainer 1314 does not cause additional rotation of introducermember retainer 1330.

As shown in the delivery configuration illustrated in FIGS. 15A-15B,continued rotation of piercing member retainer 1314 causes piercingmember 1316 to pierce pierceable seal 1326, thus opening a flow pathfrom the drug container 1050, through piercing member 1316. Piercingmember 1316 may be in fluid communication with insertion mechanism 200,for example by a fluid conduit, to allow for delivery of the fluid drugto the patient. As shown in FIGS. 19A-19B, in this configuration, tooth1314F may engage cap 1354 and/or connection hub 1312 to preventretraction of piercing member 1316.

FIG. 23 shows an exploded view of another embodiment of a fluid pathwayconnector 2300. The fluid pathway connector 2300 includes connection hub2312, introducer member 2320, introducer member retainer 2330, piercingmember 2316, piercing member retainer 2314, and, optionally, blockingaspect 2356. Additionally, first film 2318 may be provided such that itmaintains the aseptic condition of at least a portion of the fluidpathway connector. The fluid pathway connector may also include ringseal 2352 and septum 2348 configured to maintain the aseptic conditionof at least a portion of the fluid pathway connector as described above.Blocking aspect 2356 may be configured with an interlock 2338 engagingconnection hub 2312 at coupling aspect 2312H. Additionally, oralternatively, blocking aspect 2356 may be configured to engage anaspect of housing 12. Blocking aspect 2356 may be configured forrotation about these engagement points.

FIG. 24A shows the drug container 50 and fluid pathway connector 2300 inan unactuated configuration, prior to assembly. As will be understoodfrom the above discussion, this assembly step may take place in anuncontrolled or less controlled environment than that required for priorart designs. In order to mount the fluid pathway connector 2300 to thecrimp cap 2324 coupling the pierceable seal 2326 to the barrel 2058, abarrel-engaging aspect may include one or more flex arms 2312E of theconnection hub 2312, which engage the pierceable seal 2326 or crimp cap2324. FIG. 23B-23D show isometric views of the stages of operation ofthe fluid pathway connector 2300 once mounted to the drug container2050.

Initially, in the unactuated configuration illustrated in FIG. 24B,blocking aspect 2356 is initially engaged with piercing member retainer2314 such that blocking aspect 2356 prevents translation of piercingmember retainer 2314 toward drug container 2050. Additionally, oralternatively, one or more arms 2330E of introducer member retainer 2330(see FIG. 29) are initially disposed in one or more primary windows2312) of connection hub 2312 (see FIG. 28). This engagement may furtherprevent inadvertent activation of the fluid pathway connector. Forexample, in at least one embodiment, arms 2330E are configured toprovide sufficient flexural stiffness to resist disengagement fromprimary windows 2312) and prevent inadvertent activation. Application ofsufficient force for activation will cause arms 2330E to disengage fromprimary windows 2312J, allowing translation of introducer memberretainer 2330.

Upon activation, blocking aspect 2356 is displaced, for example byrotating about axis C. After displacement of blocking aspect 2356,piercing member retainer 2314 is able to translate toward drug container2050 in response to application of a driving force from an insertiondriver, such as the rotational biasing member 2210 shown in FIG. 31.FIG. 31 is a detail view showing one method of actuating the fluidpathway connector 2300. As shown, rotational biasing member 2210 isinitially held in a compressed or energized state. A first end ofrotational biasing member 2210 is engaged with an aspect of fluidpathway connector 2300, here piercing member retainer 2314. Further, ablocking aspect 2356, such as a rotatable latch, prevents de-energizingof rotational biasing member 2210 and, hence, activation of fluidpathway connector 2300. To activate the fluid pathway connector 2300,the blocking aspect 2356 may be displaced such that it no longerrestricts de-energizing of rotational biasing member 2210. As such, upondisplacement of the locking aspect 2356, rotational biasing member 2210at least partially de-energizes and causes the fluid pathway connector2300 to open a fluid path to the drug container 2050, fluidly couplingthe drug container 2050 to the needle insertion mechanism 200 via thefluid pathway connector 2300 and a sterile fluid conduit 30 coupled tothe piercing member 2316 and the needle insertion mechanism 200.Displacement of the blocking aspect 2356 may occur in response todepression, by the user, of activation mechanism 14 or, alternatively,may be controlled by interaction with a separate mechanism.

Returning now to FIGS. 24B-27B, initially, as is described furtherhereinafter, piercing member retainer 2314 and introducer memberretainer 2330 move together toward drug container 2050. FIG. 24C showsthe fluid pathway connector in the actuated configuration, that is,after introducer member 2320 pierces first film 2318 and second film2322. After piercing of first film 2318 and second film 2322, introducermember 2320 is restricted from further movement. In one embodiment, arms2330E of introducer member retainer 2330 are positioned within one ormore secondary windows 2312K, in this configuration. This engagement maylock the introducer member retainer in place, preventing inadvertenttranslation toward or away from the drug container. Continuedtranslation of piercing member retainer 2314 causes piercing member 2316to pierce pierceable seal 2326 to open a fluid flow path from drugcontainer 2050. This delivery configuration is shown in FIG. 24D.

FIGS. 25A and 25B show cross-sectional views of the fluid pathwayconnector in the initial, unactuated configuration. As can be seen inthese figures, blocking aspect 2356 is engaged with piercing memberretainer 2314 to prevent translation of piercing member retainer 2314toward the drug container. Piercing member 2316 is disposed at leastpartially within introducer member 2320. As shown, in this or anyembodiment, introducer member 2320 may be an integral portion ofintroducer member retainer 2330. Introducer member 2320 and piercingmember 2316 are both at least partially disposed in sterile cavity2312A, which is defined by connection hub 2312, first film 2318, ringseal 2352, and septum 2348. Shoulder 2314H of piercing member retainer2314 is in contact with extensions 2330D of introducer member retainer2330. Extensions 2330D are configured to be relatively flexible aspectsof introducer member retainer 2330. However, in the initialconfiguration, extensions 2330D are prevented from flexing by contactwith connection hub 2312. Hence, initially, translation of piercingmember retainer 2314, toward drug container 2050, causes commensuratetranslation of piercing member retainer 2314.

FIGS. 26A-26B show the fluid pathway connector 2300 in an intermediate,actuated configuration. In this configuration, blocking aspect 2356 hasbeen displaced such that it does not restrict translation of piercingmember retainer 2314. Introducer member 2320 has pierced first film 2318and second film 2322 and piercing member 2316 is positioned adjacent topierceable seal 2326. Also, in this configuration, extensions 2330D arepositioned adjacent to recesses 2312L of connection hub 2312. Hence,extensions 2330D are no longer restricted from flexing outward (i.e., inthe direction of the hatched arrows in FIG. 26B). Because extensions2330D are able to flex outward, into recesses 2312L, additionaltranslation of piercing member retainer 2314 causes shoulders 2314H todisengage from extensions 2330D. This allows piercing member retainer2314 to translate toward drug container 2050 without causing translationof introducer member retainer 2330. As shown in the deliveryconfiguration of FIGS. 27A-26B, this allows piercing member 2316 topierce pierceable seal 2326 and open the fluid flow path from the drugcontainer 2050.

In some embodiments, an additional film or seal may be present at thetip of introducer member 320, 1320, 2320 sealing the lumen of theintroducer member and, thereby, further isolating the lumen of theintroducer member and, hence, the piercing member in order to maintainthe aseptic condition of the piercing member. This film may remainintact as the introducer member pierces first film 318, 1318, 2318 andsecond film 322, 1322, 2322. This may further prevent any microbes orother contaminants that are present on the surfaces of the seals fromcoming in contact with the piercing member.

In at least one other embodiment, the first and second films are removedfrom the fluid pathway connector and drug container just prior tomounting of the fluid pathway connector 300 to the drug container 50.Prior to removal of the films, their placement maintains the sterilityof the pierceable seal of the drug container and cavity 312A. Connectionhub 312 and drug container 50 may be configured such that connection ofthe connection hub to the barrel provides a sealing engagement tomaintain the aseptic condition of the pierceable seal and piercingmember. In such an embodiment, connection hub 312 and/or drug container50 may include an elastomeric aspect which is configured to providesealing engagement.

In another embodiment, after mounting of connection hub 312 to drugcontainer 50, the cavity 312A and pierceable seal 326 may be sterilizedusing UV sterilization. The connection hub 312 may be in sealingengagement with the drug container such that after sterilizationmicrobes and other foreign elements are unable to contact the asepticsurfaces. In such embodiments, at least a portion of the connection hubmay be constructed from a substantially translucent material, such asglass.

In each of the embodiments described herein, the connection hub,piercing member retainer, and/or the introducer member retainer mayinclude one or more features to prevent the inadvertent activation ofthe fluid pathway connector during assembly, storage, transportation,and handling. These features may prevent activation unless a force abovea threshold value is applied. These features may, for example, includeflexible aspects or frangible aspects which are displaced or severedupon application of a force above the threshold.

In addition to the advantages described above, the insertion mechanismsdescribed herein may also be capable of terminating flow of medicamentto the target tissue by disconnecting the fluid path. This may be animportant safety feature to protect the patient. For example, somemedicaments, such as insulin, can be dangerous, and potentially evendeadly, when administered in too large a quantity and/or at too rapid ofa rate. By providing such automatic safety stop mechanisms, so-called“run-away” delivery of medicament may be prevented, thereby ensuring thesafety of the patient. While the methods and associated structures forterminating flow may be discussed with regard to one or more specificinsertion mechanisms disclosed herein, it will be appreciated that themethod and associated structures may be utilized or adapted for any ofthe fluid pathway connector assemblies disclosed herein or within thespirit and scope of this disclosure.

An interruption in delivery of medicament through the fluid pathwayconnector may be triggered, for example, by an error in delivery of themedicament or by an input from the user. For example, the user mayrealize that they have already taken their drug dose and wish to pauseor terminate drug delivery from the device. Upon such user input to thedevice, the delivery of the drug can be stopped and/or the fluidpassageway through the piercing member may be terminated by retractionof the piercing member to a retracted position, as described below.

Additionally or alternatively, the device may pause or terminate drugdelivery if it receives an error alert during operation. For example, ifthe drive mechanism is not functioning correctly, the fluid pathwayconnector may be triggered to retract the piercing member from thepierceable seal to terminate drug delivery through the fluid pathwayconnector to prevent over-delivery of a medication. This capability ofthe fluid pathway connector provides a valuable safety feature for drugdelivery to a target.

In some embodiments, retraction is activated upon removal of the drugdelivery device from the target tissue. In other embodiments, retractionis activated if it is determined that an error has occurred in thedelivery of the substances to the target tissue. For example, anocclusion of the drug delivery pathway which prevents the flow ofmedicament may be detected by a sensing function of the drug deliverypump. Upon the sensing of the occlusion an electrical or mechanicalinput may be used to initiate retraction of the needle.

Additionally or alternatively, one or more biasing members may beincluded to disconnect the fluid pathway connector. This may provide adesirable safety feature, to disconnect the fluid pathway upon signalingof an error condition either automatically by the drug delivery pump orupon action by the user. For example, a locking aspect may initiallyrestrain a secondary biasing member from expanding from its originalenergized state. Upon activation of the locking aspect, the secondarybiasing member is caused to de-energize from its original position and,thereby, act upon and axially translate the piercing member retainer todisconnect the piercing member from the pierceable seal. Once the fluidpathway connector is disconnected, flow of drug fluid is restricted orblocked between the drug container and the fluid conduit to limit orprevent fluid flow to the needle insertion mechanism and into thetarget. As described herein, the disconnection may be triggered by anumber of operations, automatically by the system and/or upon direct orindirect user initiation, as an added safety precaution to preventover-delivery of the drug fluid to the target.

One such embodiment is shown in FIGS. 32A and 32B. As shown in FIG. 32A,secondary biasing member 362 is initially restrained between connectionhub 312 and one or more release arms 360A of locking aspect 360. Lockingaspect 360 is disposed against the proximal face of connection hub 312with one or more release arms extending in the distal direction. In theevent of a fault in the operation of the drug delivery device, or uponactivation by the user, locking aspect 360 is caused to rotate aboutaxis A from the position shown in FIG. 32A to the position shown in FIG.32B. The rotation may be caused by contact of a throw arm withactivation arm 360B, for example. As locking aspect 360 is rotated, eachof the one or more release arms 360A contact a ramped surface 312M ofconnection hub 312. The contact with ramped surface 312M causesdisplacement of the one or more release arms 360A in an outwardly radialdirection or, alternatively, fracture of the one or more release arms360A. As a result, secondary biasing member 362 is able to decompress ordeenergize. Secondary biasing member 362 comes into contact withpiercing member retainer 314 and causes piercing member retainer 314 totranslate in the distal direction. This translation causes the piercingmember to be withdrawn from the pierceable seal. Hence, no additionalmedicament will be delivered through the piercing member, therebyterminating delivery to the patient. As shown in FIG. 32B, afterrotation, each of the one or more release arms 360A may flex radiallyoutward to permit the secondary biasing member 362 to deenergize, andthen return radially inward to be disposed in a notch 312N of theconnection hub. Locking aspect 360 may thereby be prevented from anyfurther rotation.

Any of the illustrated embodiments may be equipped with such a safetyfeature. Alternatively, a component of the drug delivery device maydirectly engage a portion of the fluid pathway connector to withdraw thepiercing member from the pierceable seal. For example, a slide or throwarm may contact piercing member retainer 2314, displacement of the slideor throw arm causing displacement of piercing member retainer 2314 towithdraw the piercing member from the pierceable seal.

Withdrawal of the piercing member from the pierceable seal may beactivated in the event of, for example, failure or loss of tension inthe tether, failure of the drive mechanism, removal of the drug deliverydevice from the target tissue, or activation by the user. The safetymechanism may be purely mechanical or, alternatively, may include thepower and control system. For example, an electrical signal from thepower and control system may initiate withdrawal of the piercing memberfrom the pierceable seal.

It will be appreciated from the above description that the fluid pathwayconnector assemblies and drug delivery devices disclosed herein providean efficient and easily-operated system for automated drug delivery froma drug container. The novel devices of the present disclosure providecontainer connections maintain the aseptic condition of the fluidpathway, and drug delivery pumps which incorporate such fluid pathwayconnector assemblies to drug containers. Such devices are safe and easyto use, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. Because the fluid path is disconnecteduntil drug delivery is desired by the user, the aseptic condition of thefluid pathway connector, the drug container, the drug fluid, and thedevice as a whole is maintained. These aspects provide highly desirablestorage, transportation, and safety advantages to the user. Furthermore,the novel configurations of the fluid pathway connector assemblies anddrug delivery devices of the present disclosure maintain the asepticcondition of the fluid path throughout operation of the device. Becausethe path that the drug fluid travels within the device is entirelymaintained in an aseptic condition, only these components need besterilized during the manufacturing process. Such components include thedrug container of the drive mechanism, the fluid pathway connector, thesterile fluid conduit, and the insertion mechanism. In at least oneembodiment, the power and control system, the assembly platform, theactivation mechanism, the housing, and other components of the drugdelivery device do not need to be sterilized. This greatly improves themanufacturability of the device and reduces associated assembly costs.Accordingly, the devices of the present disclosure do not requireterminal sterilization upon completion of assembly. A further benefit isthat the components described herein are designed to be modular suchthat, for example, housing and other components of the pump drug mayreadily be configured to accept and operate connection hub 312, 1312,2312, or a number of other variations of the components describedherein.

Assembly and/or manufacturing of fluid pathway connector 300, 1300,2300, drug delivery pump 10, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The fluid pathway connector and drug container may be assembled in anumber of methodologies. In one method of assembly, the drug container50 may be assembled and filled with a fluid for delivery to the target.The drug container 50 includes a cap 324, a pierceable seal 326, abarrel 58, and a plunger seal 60. The plunger seal 60 may be insertedinto barrel 58. The barrel 58 may be filled with a drug fluid throughthe open distal end prior to insertion of the pierceable seal at theopen distal end of the barrel 58. The pierceable seal 326 may then befixedly engaged between the cap 324 and the barrel 58, at a distal endof the barrel 58. In this way, the drug container can be filled andsealed using standard fill-finish processes and equipment. For example,drug container 50 may be filled and sealed using processes and equipmentcommonly employed in the filling and sealing of standard vials.Additionally, cap 324 may be a crimp cap similar to those commonly usedin such processes. Before or after applying cap 324, second seal or film322 may be applied to the distal face of drug container 50.

Piercing member 316 may be fixedly engaged with piercing member retainer314. Shaft 314A of piercing member retainer 314 may be inserted throughcentral bore 334B of plate 334 and interlock 338 may engage piercingmember retainer 314 such that biasing member 336 is prevented fromdecompressing. Introducer member 320 may be fixedly connected tointroducer member retainer 330. Additionally, sterile boot 340 may beconnected to introducer member retainer 330. Introducer member retainer330 may be positioned within piercing member retainer 314 such thatpiercing member 316 is at least partially disposed within lumen 320A ofintroducer member 320. Connection hub 312 may then be connected to plate334 by inserting snaps 312C through passages 334A. In this position, aportion of introducer member 320 is disposed within cavity 312A andsterile boot 340 is engaged with connection hub 312. Second film 322 maybe placed over aperture 312B of connection hub 312 to define cavity312A. Additionally, during assembly, the fluid conduit may be fluidlyconnected to piercing member 316. The insertion mechanism 200 may beassembled and attached to the other end of the fluid conduit. The fluidpathway connector may then be assembled to drug container 50. Theconnection of the fluid pathway connector to the drug container may ormay not occur in a clean room or sterile environment. Because first film318 and second film 322 maintain the aseptic condition of pierceableseal 326 and cavity 312A, respectively, the flow path is not exposed tocontaminants.

The steps of assembly may, optionally, also include the step ofdisposing a locking aspect against the proximal face of the connectionhub. The steps of assembly may also include disposing a secondarybiasing member concentrically around a portion of the connection hubsuch that the secondary biasing member is retained in a compressed orenergized state by the locking aspect.

In the embodiment shown in FIGS. 12A-22, assembly may include the stepsoutlined above and may also include additional or different steps. Theadditional or different steps may include connection of cap 1354 toconnection hub 1312 such that ring seal 1352 is positioned betweenconnection hub 1312 and cap 1354. The additional or different steps mayalso include placing piercing member retainer 1314 and introducer memberretainer 1330 on shaft 1342 such that they are able to rotate aboutshaft 1342. Additionally, the steps may include fixedly engagingintroducer member 1320 to first sleeve 1344 and engaging first sleeve1344 to second sleeve 1346 such that septum 1348 is positioned betweenthe sleeves. The steps may also include fixedly engaging piercing member1316 to keeper 1350.

The embodiment shown in FIGS. 23-30 may also be assembled using any ofthe steps outlined above and may also include additional or differentsteps. The additional or different steps may include, for example,coupling a blocking aspect with the connection hub at a coupling aspectof the connection hub.

The drive mechanism 100 may be attached to the proximal end of the drugcontainer 50. Certain components of this sub-assembly may be mounted tothe assembly platform 20 or directly to the interior of the housing 12,while other components are mounted to the guide 390 for activation bythe user.

Manufacturing of a drug delivery device includes the step of attachingboth the fluid pathway connector and drug container, either separatelyor as a combined component, to an assembly platform or housing of thedrug delivery device. The method of manufacturing further includesattachment of the drive mechanism, drug container, and insertionmechanism to the assembly platform or housing. The additional componentsof the drug delivery device, as described above, including the power andcontrol system, the activation mechanism, and the control arm may beattached, preformed, or pre-assembled to the assembly platform orhousing. An adhesive patch and patch liner may be attached to thehousing surface of the drug delivery device that contacts the targetduring operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; actuating a fluid pathwayconnector; and actuating a power and control system to activate a drivecontrol mechanism to drive fluid drug flow through the drug deliverydevice, wherein actuating the fluid pathway connector causes a piercingmember to penetrate a pierceable seal thereby opening a fluid path froma drug container to the fluid pathway connector. The method may furtherinclude the step of: engaging an optional on-body sensor prior toactivating the activation mechanism. Furthermore, the method ofoperation may include translating a plunger seal within the drivecontrol mechanism and drug container to force fluid drug flow throughthe drug container, the fluid pathway connector, a sterile fluidconduit, and the insertion mechanism for delivery of the fluid drug tothe target.

IV. Additional Embodiments of Fluid Pathway Connector

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, may be configured to incorporate the embodiments of the fluidpathway connector described below in connection with FIGS. 33A-33C. Theembodiments of the fluid pathway connector described below in connectionwith FIGS. 33A-33C may be used to replace, in its entirety or partially,the above-described fluid pathway connector 300 or 6300, or any otherfluid pathway connector described herein, where appropriate.

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 8000, the fluid pathway connector 8300 isenabled to connect the sterile fluid conduit 8030 to the drug containerof the drive mechanism 8100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 8100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe patient. In one such embodiment, the fluid pathway connector may besubstantially similar to that described in International PatentApplication No. PCT/US2012/054861, which is included by reference hereinin its entirety for all purposes. In such an embodiment, a compressiblesterile sleeve may be fixedly attached between the cap of the drugcontainer and the connection hub of the fluid pathway connector. Thepiercing member may reside within the sterile sleeve until a connectionbetween the fluid connection pathway and the drug container is desired.The sterile sleeve may be sterilized to ensure the sterility of thepiercing member and the fluid pathway prior to activation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Applications No.PCT/US2013/030478 or No. PCT/US2014/052329, for example, which areincluded by reference herein in their entirety for all purposes.According to such an embodiment, a drug container may have a drugchamber within a barrel between a pierceable seal and a plunger seal. Adrug fluid is contained in the drug chamber. Upon activation of thedevice by the patient, a drive mechanism asserts a force on a plungerseal contained in the drug container. As the plunger seal asserts aforce on the drug fluid and any air/gas gap or bubble, a combination ofpneumatic and hydraulic pressure builds by compression of the air/gasand drug fluid and the force is relayed to the sliding pierceable seal.The pierceable seal is caused to slide towards the cap, causing it to bepierced by the piercing member retained within the integrated sterilefluid pathway connector. Accordingly, the integrated sterile fluidpathway connector is connected (i.e., the fluid pathway is opened) bythe combination pneumatic/hydraulic force of the air/gas and drug fluidwithin the drug chamber created by activation of a drive mechanism. Oncethe integrated sterile fluid pathway connector is connected or opened,drug fluid is permitted to flow from the drug container, through theintegrated sterile fluid pathway connector, sterile fluid conduit, andinsertion mechanism, and into the body of the patient for drug delivery.In at least one embodiment, the fluid flows through only a manifold anda cannula and/or needle of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery.

In a preferred embodiment, the sterile fluid pathway connector isinitiated by movement of the needle insertion mechanism, which itself isinitiated by the multi-function drive mechanism. Additionally oralternatively, the sterile fluid pathway connector is initiated bymovement directly of the multi-function drive mechanism. For example,the multi-function drive mechanism may include a rotational gear, suchas the star gear described in detail herein, that acts concurrently orsequentially to control the rate of drug delivery, to actuate the needleinsertion mechanism, and/or initiate the sterile fluid pathwayconnector. In one particular embodiment, shown in FIGS. 33A-33C, themulti-function drive mechanism performs all of these steps substantiallyconcurrently. The multi-function drive mechanism rotates a gear thatacts upon several other components. The gear acts on a gear assembly tocontrol the rate of drug delivery, while also contacting a needleinsertion mechanism to introduce a fluid pathway into the patient. Asthe needle insertion mechanism is initiated, the sterile fluidconnection is made to permit drug fluid flow from the drug container,through the fluid conduit, into the needle insertion mechanism, fordelivery into the patient as the gear and gear assembly of themulti-function drive mechanism control the rate of drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 8300 and the sterile fluid conduit 8030 are providedhereinafter in later sections in reference to other embodiments.

V. Other Embodiments of Fluid Pathway Connector

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B and 33A-33C, may be configured to incorporate the embodiments ofthe fluid pathway connector described below in connection with FIGS.34A-42. The embodiments of the fluid pathway connector described belowin connection with FIGS. 34A-42 may be used to replace, in its entiretyor partially, the above-described fluid pathway connector 300, 6300, or8300, or any other fluid pathway connector described herein, whereappropriate.

In the processes of filling drug containers and other drug deliverydevices, it is sometimes necessary to connect two or more sterilecomponents or subassemblies. For example, wearable injectors or drugpumps may include a drug container which may be filled with a fluid drugusing standard pharmaceutical fill-finish processes. After filling ofthe drug container, it may be necessary to connect the drug container toone or more additional components or subassemblies such that a fluidcommunication may be established between the drug container and thesecomponents. Maintaining the fluid path in an aseptic condition iscritical, preventing the introduction of harmful microbes to the drugand/or fluid pathway. The connection of two or more aseptic componentsor subassemblies is typically performed in an aseptic environment, suchas a clean room, thereby ensuring that no harmful microbes areintroduced to the assembly. This, however, may lead to increased cost tomanufacture the drug delivery devices

Embodiments of the present disclosure allow aseptic connections to bemade between two or components or subassemblies in a septic environment.As seen in FIGS. 34A-34C, the connection hub 310 of a fluid pathwayconnector (e.g., fluid pathway connectors 300, 6300, and/or 8300) may beconnected to a drug container 350. FIG. 34A shows these components priorto connection. A first film 318 is in place on connection hub 312. Firstfilm 318 covers aperture 312B of connection hub 312 and preventsmicrobes from entering cavity 312A through aperture 312B, therebymaintaining cavity 312B and piercing member 316 in an aseptic condition.Piercing member 316 is partially disposed in cavity 312A and at leastpartially disposed in retainer 314. The piercing member may be a hollowneedle. Retainer 314 is engaged with connection hub 312 and may beconfigured for translation with respect to the connection hub in adirection parallel to the long axis of piercing member 316. The retainermay include one or more locking arms 314A which may engage one or morefirst recesses 312C in connection hub 312. The locking arms may includeprotrusions at their lower end, which in the locked position are atleast partially disposed in the upper recesses. The engagement of theflex arms maintains the spatial relationship of the retainer and theconnection hub.

The drug container 350 may include a crimp cap 324 that maintains aconnection between a pierceable seal 326 and a barrel (not shown). Thepierceable seal maintains the fluid drug within the barrel and preventsmicrobes and other substances from entering the drug chamber. A recess328 is formed by the geometry of the pierceable seal. A second film 322is affixed to the drug container such that it encloses recess 328,thereby maintaining recess 328 in an aseptic condition. The first andsecond films may be constructed of any material capable of providing thebarrier properties required to maintain the aseptic condition of theassociated surfaces. In a preferred embodiment, the films areconstructed from a foil material. Alternatively, the films may be anytype of sterilizable membrane, film, or foil. Additionally, the film maybe removable and/or pierceable as well as breathable and/or permeable.

An adhesive may be applied to the exterior surfaces of both first film318 and second film 322 prior to joining the fluid pathway connector andthe drug container 350. The adhesive may contain antimicrobial,antibacterial, and antiviral compounds to limit or reduce the number ofsuch substances on the surface of the seals. During connection, flexarms 312E may engage crimp cap 324 or another portion of the drugcontainer 350, thereby limiting axial translation of the fluid pathwayconnector with respect to the drug container 350. In this position,first film 318 and second film 322 are in contact with, or in closeproximity to, one another. If an adhesive is present on the faces of oneor more of the films the films may be bonded together.

After the fluid pathway connector and drug container 350 are joined, theretainer 314 may be translated axially with respect to the connectionhub. Translation of the retainer causes locking arms 314A to flex andbecome disengaged from first recess 312C. Translation of the retainercauses needle 316 to also translate. This translation causes the needleto pierce first film 318 and second film 322. After translation of theretainer, the piercing member is at least partially disposed in recess328 of pierceable seal 326. The retainer may be further translated,leading to the piercing of pierceable seal 326 by piercing member 316.After piercing of the pierceable seal a fluid path is established fromthe drug container and through the needle. The needle may also be influid communication with a conduit, the conduit being configured tocarry the fluid contents to a delivery mechanism such as an insertionmechanism for delivery to a patient. Piercing of the first and secondfilms may occur at the time of assembly. Alternatively, the piercing ofthe films may occur at or near the time-of-use of the drug deliverydevice. Piercing of the pierceable seal at or near the time-of-use maybe initiated, by the patient, by interaction with an activationmechanism.

In some embodiments, the end of the piercing member may remain disposedwithin cavity 328 until time-of-use. The pierceable seal may beconfigured such that, in response to hydraulic and/or pneumatic pressurewithin the drug chamber, it deforms and is caused to come into contactwith the piercing member. This deformation of the pierceable seal leadsto the piercing of the seal by the piercing member.

FIGS. 35A-35D show an embodiment in which a connection hub 1312 of afluid pathway connector is connected to a drug container such that thelong axis of the piercing member 1316 is orthogonal to the long axis ofthe drug barrel 1330 of the drug container. As seen in FIG. 35B, flexarms 1312E engage a portion of cap 1324 to securely attach the fluidpathway connector to the drug container. The fluid pathway connector mayfurther include insert 1332 disposed within connection hub 1312.Extension 1314D of retainer 1314 may be sealingly engaged with insert1332 and be configured for axial translation with respect to the insert.Protrusions 1314B of retainer 1314 are initially disposed in firstrecesses 1312C of connection hub 1312. In this position, the piercingend of piercing member 1316 is disposed within insert 1332. FIG. 35Cshows a cross-sectional view of the drug container and fluid pathwayconnector after assembly and before connection of the fluid path. Asseen in the cross-section, cap 1324 may contain side port 1324A whichallows the piercing member to access the pierceable seal. Also shown inFIG. 35C is conduit port 1314C which may be configured to allow aconduit to be connected to the retainer. This conduit may provide afluid path that connects the drug container to a delivery mechanism fordelivery of the fluid drug to the patient. FIG. 35D is a cross-sectionshowing the assembly in an open fluid path configuration. As shown,retainer 1314 has been displaced toward the center axis of the drugcontainer. Protrusions 1314B of flex arms 1314 have disengaged fromfirst recesses 1312C and have engaged second recesses 1312D. Piercingmember 1316 has pierced first film 1318, second film 1322, andpierceable seal 1326. The piercing of each of these may occur at time ofuse upon patient initiation. Alternatively, the first and second filmmay be pierced at time of assembly. This creates a fluid path from thedrug container, through the piercing member, conduit, and insertionmechanism for delivery to the patient. The connection of the fluidpathway connector such that the long axis of the piercing member isorthogonal to the long axis of the drug container may allow for morecompact packaging in a drug delivery device.

In other embodiments, shown in FIGS. 36A-36D, the piercing memberincludes an inner piercing member 2316A and an outer piercing member2316B. The inner piercing member 2316A is disposed within the hollowouter piercing member 2316B. After connection of the connection hub 2312to the drug container 2330, the outer piercing member 2316B pierces thefirst film 2318 covering terminal end of the connection hub 2312 and thesecond film 2318 covering the terminal end of the drug container 2330,while maintaining the inner piercing member 2316A within its hollowinner cavity. The piercing may be caused by joint motion of the piercingmembers 2316A and 2316B toward the drug container or, alternatively, maybe caused by the drug container displacing the connection hub, therebyexposing the outer piercing member 2316B. Because the inner piercingmember 2316A does not contact the first and second films 2318 and 2322,any contaminants present on the surface of the films 2318 and 2322 arenot in contact with the inner piercing member 2316A. After piercing thefilms 2318 and 2322 the outer piercing member is retracted, therebyexposing the inner piercing member 2316A. In this position, shown inFIG. 36C, the end of the inner piercing member 2316A is disposed in thecavity 2328 created by the pierceable seal 2326. In response toincreased hydraulic and/or pneumatic pressure within the drug containerthe pierceable seal 2326 may deform, as shown in FIG. 36D. Thedeformation of the pierceable seal 2326 causes the inner piercing member2316A to pierce the pierceable seal 2326, thereby creating a fluid pathfrom the drug container 2330 through the inner piercing member 2316A fordelivery to the patient.

As shown in the alternative embodiment of FIGS. 37-38, the fluid pathwayconnector may include an elastomeric component 3334. At least a portionof the outer piercing member 2316B may be embedded in the elastomericcomponent 3334. The outer piercing member 2316B may be embedded in theelastomeric component 334 while in an aseptic environment. The asepticcondition of the embedded portion of the outer piercing member 2316B ismaintained when the fluid path connection mechanism is transferred to aseptic environment due to the sealing engagement of the outer piercingmember 2316B with the elastomeric component 3334. Hence, after mountingthe fluid pathway connector to the drug container, the fluid pathwayconnector may be transformed to the open configuration by initiallypiercing of the first and second films 2318 and 2322 with the outerpiercing member 2316B, and then piercing the pierceable seal 3324 withthe inner piercing member 2316A by moving the inner piercing member2316A relative to the outer piercing member 2316B while keeping theouter piercing member 2316B stationary. In this way, the inner piercingmember 2316A is not contaminated by touching the non-sterile exteriorsurfaces of the first and second foils 2318 and 2322. In alternativeembodiments, the outer piercing member 2316B may be the sole piercingmember and/or may pierce the pierceable seal 3324 in addition to thefirst and second films 2318 and 2322. As seen in the further alternativeembodiment of FIGS. 38A-D, the first film 2318 and/or the second film2322 may further include an adhesive containing antimicrobial agents asdescribed above. Initially, the antimicrobial adhesive of the first film2318 may be covered by a removable liner 2319 and the antimicrobialadhesive of the second film 2322 may be covered by a removable liner2323. Prior to assembling the first film 2318 in engagement with thesecond film 2322, the removable liners 2319 and 2323 may be removed.This presence of the antimicrobial adhesive on the exterior surfaces ofthe first and second films 2318 and 2322 inhibits or preventscontamination of those surfaces if this step of the assembly isperformed in a non-sterile environment.

In some embodiments, as shown in FIGS. 39A-B, an additional film or seal4336 may be present on the outer piercing member 4316B which furtherisolates the inner cavity of the outer piercing member 4316B and hencethe inner piercing member 4316A. This seal 4336 may remain intact as theouter piercing member pierces first film 4318 and second film 4322. Thismay prevent any microbes that are present on the surfaces of the sealsfrom coming in contact with the inner piercing member. After piercingthe first and second films 4318 and 4322 the translation of the outerpiercing member 4318B may be restricted prior to the outer piercingmember piercing the piercable seal 4326. The inner piercing member 4316Acontinues to translate toward the drug container 2330 and pierces thefirst and second films 4318 and 4322 and the pierceable seal 4326,thereby opening the fluid path. Furthermore, in the embodiment shown inFIGS. 39A-B, an antimicrobial adhesive 4325 may initially cover theexterior surface(s) of the first film 4318 and/or the second film 4322.

In other embodiments, shown in FIGS. 40A-C, the first and second filmsare removed from the fluid pathway connector and drug container justprior to mounting of the fluid pathway connector. Prior to removal ofthe films, their placement maintains the sterility of the pierceableseal of the drug container and the face of the elastomeric component ofthe fluid pathway connector. Except for the removal of the first andsecond films prior to connection of the fluid pathway connector and thedrug container and the omission of the outer piercing member 2316B, theembodiment shown in FIGS. 40A-C includes same or similar elements as theembodiment shown in FIGS. 37A-C. Thus, same reference numerals are usedto indicate same or similar elements in both sets of figures. It isnoted that the outer piercing member 2316B of the embodiment shown inFIGS. 37A-C can be implemented in an alternative version of theembodiment shown n FIGS. 40A-C. Also, it is noted that the elastomericcomponent 3334 of the FIGS. 40A-C embodiment, unlike the elastomericcomponent 3334 of the FIGS. 37A-C embodiment, includes a recess orcavity 2327 configured to receive and form a tight fit (e.g., anairtight interference or press fit) with a distal end 2329 of the drugcontainer 2330. This tight fit may prevent the ingress of contaminantsand thereby maintain sterility of the interface between the drugcontainer and the fluid pathway connector. In some embodiments, thedistal end 2329 of the drug container 2330 may be inserted into therecess 2327 and the elastomeric component 3334 under non-sterile oraseptic conditions so that contaminants are not trapped between distalend 2329 of the drug container 2330 and the elastomeric component 3334as the result of assembly.

As shown in the alternative embodiment of FIGS. 41A-D, the fluid pathwayconnector may also be mounted to the drug container 2330 using a glasstube 2335. After mounting, the glass tube 2335 and the surfaces of theelastomeric piercing member retainer or component 3334 and pierceableseal 3324 may be sterilized using UV sterilization (see FIG. 41C). Theglass tube may be in sealing engagement (e.g., an airtight seal) withboth the drug container 2330 and the elastomeric component 3334 of thefluid pathway connector such that after sterilization microbes and otherforeign elements are unable to enter the glass tube, thereby maintainingthe aseptic condition of the interior of the glass tube 2335. Except forthe omission of the first and second foils 2318 and 2322 and theinclusion of the glass tube 2335, the embodiment shown in FIGS. 41A-Dmay include the same or similar elements as the embodiment shown inFIGS. 40A-C. Therefore, same reference numerals are used to indicatesame or similar elements in both sets of figures.

The embodiment shown in FIG. 42 shows a connection which is madeorthogonal to the long axis of the drug container. In this embodiment, afirst film 5318 is initially in place over and maintaining the sterilityof a cavity 5312A of the connection hub 5312. During connection, thefirst film 5318 is pierced by an insert 5340 of the drug container. Thepierced portion is retained within the concave portion 5342 of theinsert after piercing. By retaining this pierced portion within theconcave portion the non-aseptic surface of the first film is isolatedand any substances present thereon are prevented from contaminating thedrug fluid or fluid path. A second film 5322 is initially in place overan aperture 5340A in the insert 5340, maintaining the aseptic conditionof the aperture. The second film 5322 may be a rigid or elastomericcomponent which is in tight conformity to the insert such that itprevents microbes and other contaminants from entering the aperture.Upon mounting of the connection hub to the drug container the secondfilm may be displaced from its initial position, thereby allowing afluid path to be established from the drug container through the fluidpathway connector. After mounting of the connection hub to the drugcontainer the aperture 5340A in the insert 5340 is aligned with anaperture 5312B in the connection hub 5312. A pierceable seal may be inplace over one or more of the apertures which may be pierced by apiercing member to establish a fluid path. One or more snap arms mayretain the insert in position in relation to the drug barrel. The snaparms may connect to the drug barrel itself or another component of thedrug container.

VI. Additional Embodiments of Fluid Pathway Connector

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B and 33A-33C, may be configured to incorporate the embodiments ofthe fluid pathway connector described below in connection with FIGS.43-52D. The embodiments of the fluid pathway connector described belowin connection with FIGS. 43-52D may be used to replace, in its entiretyor partially, the above-described fluid pathway connectors 300, 6300, or8300, or any other fluid pathway connector described herein, whereappropriate.

As shown in the embodiment of FIGS. 43-45, the drug container 1850 mayconsist of barrel 1858, cap 1852, and pierceable seal 1856. Base 1856Aof pierceable seal 1856 may be in sealing engagement with the inside ofbarrel 1858. Cap 1852 may be fixedly engaged to the outside of barrel1858 and may retain pierceable seal 1856 in position and restrictmovement of pierceable seal 1856 with respect to barrel 1858. Cap 1852may include one or more locking arms 1852A which extend from ring 1852Bof cap 1852 substantially parallel to axis A-A and in a distaldirection. The locking arms 1852A may include a radially extendingprotrusion 1852C at or near their distal ends. The drug container mayfurther include toroidal seal 1857. In an initial configuration, shownin FIG. 43, the toroidal seal is retained between protrusions 1852B andproximal circumferential rib 1856B of pierceable seal 1856. Pierceableseal 1856 may further include distal circumferential rib 1856C whichfurther retains toroidal seal 1857. By placing the toroidal seal in thisposition when the drug container is in an aseptic environment theportion of pierceable seal 1856 in contact with the inner face oftoroidal seal 1857 (i.e., the area between the proximal circumferentialrib and the distal circumferential rib) is maintained in an asepticcondition even if the drug container is moved to a septic environment.

The fluid pathway connector 18300 includes connection hub 18310,retainer 18320, piercing member 18330, and plug seal 18330. As shown inFIG. 45A, plug seal 18330 is initially disposed within bore 18310A ofconnection hub 18310. When the fluid pathway connector is assembled, theplug seal maintains the aseptic condition of at least a portion of thefluid pathway connector by maintaining a sealing engagement with bore18310A. The retainer is disposed for sliding translation with respect toconnection hub 18310 in a direction parallel to axis B-B (shown in FIG.45D). Initially, translation of retainer 18320 may be restricted. Therestriction may be by engagement of flex arms 18320B with recesses inconnection hub 18310. Piercing member 18330 may be fixedly engaged withretainer 18320 such that translation of retainer 18320 is transferred tothe piercing member. The piercing member may be bonded, press-fit, orengaged to the retainer using other appropriate means. The piercingmember may initially be at least partially disposed within cavity 18310Dand/or aperture 18310C of connection hub 18310. Both cavities 18310D and18310C are maintained in an aseptic condition by plug seal 18340.Retainer 18320 may further include conduit connection 18320A to whichthe sterile fluid conduit 30 (see FIG. 1B) may be attached. Thisprovides a sterile fluid path from the sterile fluid pathway connectorto the insertion mechanism. Piercing member 18330 may be a hollow needlesuch that fluids may pass through the hollow interior of the piercingmember and into the sterile fluid conduit.

FIGS. 45A-D show the steps of connecting the fluid pathway connector tothe drug container. This connection may be performed in a non-asepticenvironment. In FIG. 45A, the plug seal of the fluid pathway connectoris substantially aligned with axis A-A (i.e., the plug seal 18340 isaligned with the distal end of the pierceable seal 56). FIG. 45B shows across-section view of the fluid pathway connector 18300 in contact withthe drug container. Recesses 18310B of connection hub 18310 are alignedwith locking arms 1852A, this alignment guides the installation of thefluid pathway connector and prevents rotation of the fluid pathwayconnector with respect to the drug container. As shown in FIG. 45C, asthe connection hub is translated in the proximal direction along axisA-A the plug seal 18340 is prevented from translating with theconnection hub due to contact with pierceable seal 1856. This causes theplug seal to be displaced from its position within bore 18310A.Additionally, contact of shoulder 18310E of connection hub 18310 withtoroidal seal 1857 causes the toroidal seal to translate in the proximaldirection along axis A-A. As the connection hub is translated along axisA-A only bore 18310A comes in contact with the portion of the pierceableseal which was previously covered by toroidal seal 1857. Further, as theconnection hub comes into contact with the toroidal seal thesecomponents sealingly engage such that microbes and other foreignsubstances may not come in contact with the sterile portions of thepierceable seal and fluid pathway connector. In this way the asepticcondition of the pierceable seal 1856, aperture 18310C, cavity 18310D,and piercing member 18330 are maintained during installation of thefluid pathway connector.

As seen in FIG. 45D, further proximal translation of the connection hubbrings the connection hub into contact with a portion of drug container1850, thus preventing further distal translation of the connection hub.In the embodiment shown, the connection hub contacts a portion of cap1852. When the connection hub reaches this position, the plug seal maybe removed from the assembly and discarded. Snap arms 1852A may engageone or more aspects of the connection hub and thereby prevent theconnection hub from being removed from the drug container.

After installation, the piercing member is aligned with the sterileportion of the pierceable seal which was originally engaged with thetoroidal seal. The components may be assembled into the drug deliverydevice 10 (see FIGS. 1A-1C) and remain in this configuration untilactivation of the drug pump by the user. Upon activation, the retainer18320 is translated in a direction parallel to axis B-B with respect tothe connection hub, causing translation of piercing member 18330. Due tothis translation, the piercing member comes in contact with and,subsequently, pierces the pierceable seal 1856. This opens a fluidpathway from the drug container and through the piercing member. Thefluid pathway may further include sterile fluid conduit 30 (see FIG. 1B)which is engaged with conduit connection 18320A of retainer 18320. Inthis way a sterile fluid path is provided from the drug container to theinsertion mechanism for delivery to the patient.

FIGS. 46A-46B show another embodiment of the present disclosure in whichconnection hub 181310 includes snap arms 181310F which may engage cap181052 of drug container 181050. Toroidal seal 181057 is initiallyretained between proximal circumferential rib 181056B and distalcircumferential rib 181056C of pierceable seal 181056 and is caused totranslate in the proximal direction by contact with the connection hub.After mounting of the fluid pathway connector to the drug container,opening of the fluid pathway is substantially similar as that describedabove.

FIG. 47 shows a detail view of the plug seal disposed within the bore ofthe connection hub. This shows a possible method of retaining the plugseal in position using tabs 181310G. These tabs control the location ofthe plug seal in the inner bore.

FIGS. 48-50 show additional embodiments of the disclosure illustratingalternative configurations of the cap and pierceable seal.

In the embodiment shown in FIG. 51, bore 182310A is enclosed on itsdistal face by distal film 182350 and on its proximal face by proximalfilm 182352. The proximal and distal films may be constructed from anymaterial with barrier properties sufficient to prevent the passage offoreign matter. For example, the films may be constructed from a foilmaterial. The films may be bonded or otherwise securely affixed to theconnection hub. In this way, bore 182310A is maintained in an asepticcondition.

As the fluid pathway connector is brought into contact with the drugcontainer, a portion of the drug container pierces, tears, or otherwiseremoves a portion of proximal film 182352 from the connection hub. Forexample, as shown in FIG. 51, a portion of the cap 182052 contacts theproximal film during installation and disengages a portion thereof fromthe connection hub. The disengaged portion of proximal seal 182352 maybe retained within void 182055 formed by cap 182052 and pierceable seal182056, thereby preventing the septic portion of proximal film 182352from contacting the aseptic portion of pierceable seal 182056.

Also shown in FIG. 51, seal 182057 may be configured to maintain theaseptic condition of only a portion of the circumference of pierceableseal 182056. This portion may be configured to be aligned with aperture182310C and piercing member 182330 after installation of fluid pathwayconnector 182300. During installation, seal 182057 is displaced by theconnection hub as described in reference to other embodiments. Seal182057 may be retained in position with respect to the pierceable sealby engagement of the seal with slot 182052D of cap 182052, proximalcircumferential rib 182056B, and distal circumferential rib 182056C.During displacement, the seal may translate within slot 182052D in theproximal direction.

FIGS. 52A-52D show another embodiment of a fluid pathway connector inwhich the fluid pathway connector includes first rotating disk 183360and drug container 183050 includes second rotating disk 183051. Firstrotating disk 183360 may be configured for rotation with respect toconnection hub 183310 about a central axis and further include firstopening 183360A. As shown in FIG. 52A, the first rotating disk may alsoinclude post 183360B and receptacle 183360C. Second rotating disk 183051may include complementary features to allow for alignment of the firstopening 183360A with the second opening 183051A. Second rotating disk183051 may be configured for rotation with respect to the drug containerand have second opening 183051A. One or both of the openings mayinitially be covered by a film such that the film prevents foreignmaterials from entering the openings.

As seen in FIG. 52C, during installation the first and second rotatingdisks are brought into contact such that the first and second openingsare aligned. The rotating disks may be joined through the use of anadhesive or, alternatively, may be held in contact by features such asthe snap arms described previously in relation to other embodiments.Once connected, the disks may be rotated such that they align withchimney 183053 and third opening 183310F in connection hub 183310.Chimney 183053 may be biased for axial movement in the distal direction,such as by a spring or other biasing member capable of storing energy.As shown in FIG. 52D, upon alignment with the first and second opening,the chimney translates in the distal direction, passing through both thefirst and second opening. The chimney may have a pass-through whichallows contents to flow from the drug container. In this way, a sterilefluid path is created between the drug container and the fluid pathwayconnector. The fluid pathway connector may further include a piercingmember which is configured to, upon activation by a user, pass throughthe chimney and pierce a pierceable seal of the drug container. Afterthe pierceable seal is pierced, drug fluid may pass through the piercingmember and be delivered to the patient. The piercing member may beengaged with retainer 183320. The retainer may also be configured forconnection of sterile fluid conduit 30 (see FIG. 1B) at conduitconnection 183320A. The translation of the piercing member may be causedby translation of the retainer.

In at least one embodiment, the present disclosure provides auser-initiated fluid pathway connector. The fluid pathway connectorincludes: a connection hub, a piercing member, a piercing memberretainer, and a drug container having a cap, a pierceable seal, and abarrel, wherein the piercing member is at least partially disposed in asterile chamber defined by the connection hub. The fluid pathwayconnector is configured such that it may be connected to the drugcontainer while maintaining the aseptic condition of a fluid pathway.The drug container may contain a drug fluid for delivery. The fluidpathway connector may further be in fluid communication with a conduitthat provides a fluid pathway for delivery of the fluid drug to thepatient. Upon initiation by the user, the fluid drug is deliveredthrough the fluid pathway to the body of the user. The pierceable sealincludes a seal barrier that may be penetrated, upon user initiation, bythe piercing member.

In another embodiment, the present disclosure provides a drug deliverypump with integrated sterility maintenance features having a housing andan assembly platform, upon which an activation mechanism, a fluidpathway connector, a power and control system, and a drive mechanismhaving a drug container may be mounted, said fluid pathway connectorincluding a connection hub, a piercing member, a piercing memberretainer, and a drug container having a cap, a pierceable seal, and abarrel, wherein the piercing member is at least partially disposed in asterile chamber defined by the connection hub. The fluid pathwayconnector is configured such that it may be connected to the drugcontainer while maintaining the aseptic condition of a fluid pathway.The drug container may contain a drug fluid for delivery. The fluidpathway connector may further be in fluid communication with a conduitthat provides a fluid pathway for delivery of the fluid drug to thepatient. Upon initiation by the user, the fluid drug is deliveredthrough the fluid pathway connector to the body of the user. Thepierceable seal includes a seal barrier that may be penetrated, uponuser initiation, by the piercing member.

VII. Additional Embodiments of Fluid Pathway Connector

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B and 33A-33C, may be configured to incorporate the embodiments ofthe fluid pathway connector described below in connection with FIGS.53A-68. The embodiments of the fluid pathway connector described belowin connection with FIGS. 53A-68 may be used to replace, in its entiretyor partially, the above-described fluid pathway connector 300, 6300, or8300, or any other fluid pathway connector described herein, whereappropriate.

In general, the present embodiments provide for container connectionsthat maintain the sterility of a fluid pathway and are integrated into afluid container; drug delivery devices that incorporate such sterilefluid pathway connectors to fluid containers; methods of operating suchdevices; and methods of assembling such devices. The fluid pathwayconnectors of the present embodiments provide integrated safety featuresthat ensure the sterility of the fluid pathway before, during, and afterfluid delivery. In one aspect, the fluid pathway remains disconnectedfrom the fluid container until the device has been initiated by theoperator. In another aspect, the fluid pathway maintains the sterilityof a piercing member prior to connection with the fluid container withina sterile cavity prior to activation by the operator. Upon activation bythe operator, at least a portion of a pierceable seal is translated,such as by pneumatic and/or hydraulic pressure or force within thefluid, towards a substantially fixed piercing member such that thepierceable seal is pierced and the fluid pathway is connected or openedto enable fluid flow through the fluid pathway for fluid delivery fromthe device.

A drug delivery device, such as an infusion pump or a bolus injector,may be needed to deliver a particular amount of fluid within a period oftime. For example, when delivering a drug fluid subcutaneously it isimportant to control the flow of fluid that is delivered into thepatient and to maintain the sterility of the fluid container and fluidpathway prior to activation or operation of the fluid delivery device.It may be desired that the fluid pathway connector remains disconnected,for container integrity, sterility, and other purposes, until the userhas activated the device and initiated fluid flow from a container. Somedrug delivery devices may utilize one or more active fluid pathwaycontrol mechanisms to prevent premature fluid pathway connector or drugdelivery. Other drug delivery devices are configured such that fluidpathway connector is made upon manufacture, and fluid delivery isblocked until desired by the user. Such designs do not provide thebeneficial advantages associated with maintaining container integrityand sterility of the internal components of the drug delivery device.The present embodiments provide an integrated fluid pathway connectormechanism for sterile drug delivery devices. These novel embodimentsprovide both a connection mechanism to open or connect a sterile fluidpathway between a fluid container and a fluid conduit, without addingunnecessary steps for the user. This is enabled by activation of thedrive mechanism and translation of the plunger seal, resulting inpneumatic and/or hydraulic pressure within the fluid that forcestranslation of at least a portion of a pierceable seal, causing it toimpact upon a substantially stationary piercing member, thus opening asterile fluid pathway between the fluid container and the fluid conduit.

Accordingly, the embodiments of the present disclosure provide a sterilefluid pathway connector that is integrated into a fluid container andopened, connected, activated, or otherwise enabled by the operation ofthe device and drive mechanism. The activation of the drive mechanismand the force transferred from the drive mechanism to the plunger sealis, itself, used to open a sterile fluid pathway between the fluidcontainer and the fluid conduit. Accordingly, container integrity andsterility of the fluid container may be maintained prior to and duringoperation of the device. This novel configuration also automates thesterile fluid pathway connector step, greatly reducing the complexity ofthe device and operational steps needed to be performed by the device orthe user. The novel embodiments of the present disclosure also permitflexibility in device component configurations, and reduce the layout oroverall footprint of the device because no separate sterile fluidpathway connector mechanism is needed on the cap-side of the fluidcontainer. The present embodiment may also be implemented fully orutilized in standard production of sterile fluids, including drugfill-finish processes, including applications that require the pullingof a vacuum. Additionally, the present embodiments may also integrate anumber of different status indication mechanisms into the device,including utilizing the piercing member or the plunger seal as parts ofan indication mechanism that relates status of fluid transfer from thesterile fluid container to the connector. For example, when the fluidcontainer is a drug container, such components and devices provide anend-of-dose indication coupled to the actual travel and drug deliverystatus of the plunger seal.

At least one embodiment provides for a sterile fluid pathway connectorthat includes a piercing member, a connector hub, and a pierceable seal.More specifically, at least one embodiment provides for sterile fluidconnector comprising a first portion configured to connect a sterilefluid pathway and a second portion comprising a housing configured tomount a sterile fluid container; a connector hub; a pierceable sealdisposed at least partially between the connector hub and the sterilefluid container and forming a sterile fluid chamber between theconnector hub and the pierceable seal; and a piercing member disposedwithin the connector hub capable of providing a sterile fluidcommunication between the sterile fluid chamber and the sterile fluidpathway; wherein at least a portion of the pierceable seal is configuredto transform from a non-activated state in which the pierceable seal isintact, to an activated state in which the pierceable seal is disruptedby the piercing member to create a sterile fluid communication betweenthe sterile fluid container and the sterile fluid pathway. The housingmay be further configured to recess a portion of the connector withinthe sterile fluid container. The connector hub may further comprise atleast one port or vent. The sterile fluid pathway may also include atleast one sensor configured to indicate the status of fluid transferfrom the sterile fluid container to the connector. Additionally, thesterile fluid pathway connector may include one or more flowrestrictors. In at least one embodiment, the connector hub may at leastpartially function as a fluid conduit or flow restrictor. In at leastone embodiment, the fluid pathway connector further includes a filter. Anumber of known filters may be utilized within the embodiments of thepresent disclosure, which would readily be appreciated by an ordinarilyskilled artisan. For example, the filter may comprise a permeablemembrane, semi-permeable membrane or porous membrane, which encloses thesterile cavity from the outside environment.

The piercing member is initially retained in a substantially fixedposition within a sterile cavity between the connector hub and thepierceable seal. Upon activation by the operator (e.g., a patient), atleast a portion of the pierceable seal is caused to move to a secondposition in which the pierceable seal is penetrated by the piercingmember. Force, such as pneumatic and/or hydraulic force, applied on thepierceable seal on the side opposing the sterile cavity, causestranslation of at least a portion of the pierceable seal towards thepiercing member. The translation of the pierceable seal causes it toimpact upon the substantially stationary or fixed piercing member toopen a fluid pathway through the pierceable seal. Accordingly, at leasta portion of the pierceable seal is configured to move from the firstposition to the second position by force applied by a fluid on thepierceable seal. Penetration by the piercing member of the pierceableseal upon movement of a portion of the pierceable seal from the firstposition to the second position opens a fluid pathway through thepierceable seal and the piercing member to a fluid conduit.

In at least one embodiment, the pierceable seal comprises a seal barrierthat can be penetrated by the piercing member. The piercing member mayinitially be in contact with, or adjacent to, the seal barrier.

The fluid pathway connector may further include a piercing member guide,wherein the piercing member guide is capable of engaging with ortranslating upon the connector hub. The piercing member guide mayfunction to ensure that the pierceable seal, or at least a portionthereof such as a seal barrier, properly contacts the piercing memberand translates thereupon to become pierced and open the fluid pathwaythrough the pierceable seal and piercing member to a fluid conduit.

The piercing member may be configured to pass into the connector hub andconnect to a fluid conduit. In another embodiment, the connector hub mayconnect the piercing member to the fluid conduit, and the fluid conduitmay be at least partially a part of the connector hub. In at least oneembodiment, the fluid conduit passes into the connector hub at a port inthe connector hub.

In at least one embodiment, the sterile fluid connector includes atleast one sensor configured to indicate the status of fluid transferfrom the sterile fluid container to the connector. For example, thesterile fluid pathway connector may further include one or moreinterconnects and, optionally, one or more corresponding contacts, totransmit a signal to the user. For example, the interconnect(s) may bewithin or at least partially proximal to a plunger seal translatablewithin a fluid container such that the piercing member is capable ofpenetrating the plunger seal and acting as a contact(s) for theinterconnect(s) to transmit a signal to the user. Additionally oralternatively, the interconnect(s) or the contact(s) is within or atleast partially proximal to a plunger seal translatable within a drugcontainer and the other is within or at least partially distal to thepierceable seal to transmit a signal to the user when the plunger sealand the pierceable seal are substantially in contact. Additionally oralternatively, the interconnect(s) and contact(s) are within the sterilecavity between the connector hub and pierceable seal such that releaseof pneumatic and/or hydraulic pressure at the end of fluid transferreleases interconnection to transmit or cease transmission of a signalto the user. A number of known interconnects and contacts may beutilized within the embodiments of the present disclosure, which wouldreadily be appreciated by an ordinarily skilled artisan. For example, arange of: Hall effect sensors; giant magneto resistance (GMR) ormagnetic field sensors; optical sensors; capacitive or capacitancechange sensors; ultrasonic sensors; and linear travel, LVDT, linearresistive, or radiometric linear resistive sensors; and combinationsthereof, which are capable of coordinating to transmit a signal to theuser may be utilized for such purposes.

Another embodiment provides for an integrated fluid pathway connectorand drug container having a piercing member, a connector hub, and apierceable seal integrated at least partially within a drug containerhaving a barrel and a plunger seal. The pierceable seal is translatableupon a substantially stationary piercing member, and the pierceable sealis configured to move from a first position, where the piercing memberis positioned within a sterile cavity between the connector hub and thepierceable seal, to a second position, where the pierceable seal hasbeen penetrated by the piercing member. The fluid container contains afluid chamber between the pierceable seal and the plunger seal toinitially retain a fluid, and the pierceable seal is configured to movefrom the first position to the second position by a force applied by thefluid on the pierceable seal. In at least one embodiment, the pierceableseal has a seal barrier that can be penetrated by the piercing member,and the piercing member is initially in contact with, or adjacent to,the seal barrier.

The integrated fluid pathway connector may further include a piercingmember guide piece attached to the connector hub or piercing member,wherein the piercing member guide slidably engages the connector hub orpiercing member to permit translation of the pierceable seal, or aportion thereof, in the direction of fluid exit from the connector.Translation of the pierceable seal in the direction of the fluidcontainer may be prevented by retention of a portion of the pierceableseal by, for example, a housing, such as a crimped cap, mounted to thefluid container barrel that retains the connector hub, piercing member,and pierceable seal in position during operation. Such a configurationmay be used to permit the fluid chamber of the fluid container to beevacuated, such as by vacuum, prior to filling with a fluid withoutcompromising the function of the sterile fluid pathway connector.

In at least one embodiment, the connector hub has a header with aconduit port, a chamber, and a vacuum port with a channel that leadsinto the chamber such that the sterile cavity may be evacuated throughthe channel. The conduit port may have a membrane or seal that permitsfluid flow out of the chamber, and may be capable of being plugged.Similarly, the vacuum port may be capable of being plugged, such as by apolymeric plug. Such configurations allow, for example, the sterilecavity to be evacuated to maintain both sterility and pressureequilibrium between the sterile cavity and the opposing side of thepierceable seal, or otherwise assist in maintaining the relativepositions of the components prior to or during operation of the deviceby the user.

In at least one embodiment, the pierceable seal, or at least a portionthereof, is translatable upon the piercing member and the pierceableseal is further configured to move from the second position, where thepierceable seal has been penetrated by the piercing member, to a thirdposition wherein at least one sensor indicates the status of fluidtransfer from the sterile fluid container to the connector. For example,in a third position, one or more interconnects and one or morecorresponding contacts are permitted to transmit a signal to the user.In one such embodiment, the interconnect(s) or the contact(s) is upon anaspect of a drive mechanism and the other is within or at leastpartially proximal to the plunger seal to transmit a signal to the userwhen the plunger seal and the pierceable seal are substantially incontact. Alternatively, the interconnect(s) or the contact(s) is withinor at least partially distal to the pierceable seal and the other isproximal to the connector hub to transmit a signal to the user when theplunger seal and the pierceable seal are substantially in contact.Additionally or alternatively, the interconnect(s) and contact(s) arewithin the sterile cavity between the connector hub and pierceable sealsuch that release of pneumatic and/or hydraulic pressure at end of dosereleases interconnection to transmit or cease transmission of a signalto the user. A number of known interconnects and contacts may be usedwith the present embodiments, which would readily be appreciated by askilled artisan. For example, a range of: Hall effect sensors; giantmagneto resistance (GMR) or magnetic field sensors; optical sensors;capacitive or capacitance change sensors; ultrasonic sensors; and lineartravel, LVDT, linear resistive, or radiometric linear resistive sensors;and combinations thereof, which are capable of coordinating to transmita signal to the user may be utilized for such purposes.

Yet another embodiment provides a drug delivery device with integratedsterility maintenance features comprising a housing within which anactivation mechanism, an insertion mechanism, and a fluid containerhaving a plunger seal may be mounted. The fluid container is connectedat one end to a drive mechanism and at another end to a fluid pathwayconnector. The fluid pathway connector includes a piercing member, aconnector hub, and a pierceable seal, wherein the piercing member isretained within a sterile cavity between the connector hub and thepierceable seal, and wherein the pierceable seal is configured to movefrom a first position to a second position in which the pierceable sealhas been penetrated by the piercing member. The fluid container containsa fluid chamber between the pierceable seal and the plunger seal toinitially retain a fluid, and wherein the pierceable fluid seal isconfigured to move from the first position to the second position by aforce applied by the fluid on the pierceable seal. In at least oneembodiment, the pierceable seal has a seal barrier that can bepenetrated by the piercing member, and the piercing member is initiallyin contact with, or adjacent to, the seal barrier.

The drug delivery device may further include a piercing member guideengaged with the connector hub or piercing member, wherein the piercingmember guide slidably engages the connector hub or piercing member topermit translation of the pierceable seal, or a portion thereof, in thedistal direction (i.e., towards the fluid conduit from where fluid exitsthe connector). Translation of the pierceable seal in the proximaldirection may be prevented by retention of the pierceable seal, or aportion thereof, by, for example, a housing such as a crimped capmounted to the barrel, which housing retains the connector hub, piercingmember, and pierceable seal in position during operation. Such aconfiguration may be used to permit the drug chamber of the drugcontainer to be evacuated, such as by vacuum, prior to filling with afluid without compromising the function of the sterile fluid pathwayconnector. In at least one embodiment, the connector hub has a headerwith a conduit port, a chamber, and a vacuum port with a channel thatleads into the chamber such that the sterile cavity may be evacuatedthrough the channel. The conduit port may have a filter, membrane orseal to permit or restrict fluid flow out of the chamber. Similarly, thevacuum port may be capable of being plugged, such as by a polymericplug. Such configurations may allow, for example, the sterile cavity tobe evacuated to maintain sterility, the maintenance of pressureequilibrium between the sterile cavity and the opposing side of thepierceable seal, or assist in maintaining the relative positions of thecomponents prior to or during operation of the device by a user.

In at least one embodiment, the pierceable seal is translatable upon thepiercing member or an aspect of the connector hub and is furtherconfigured to move from the second position, where the pierceable sealhas been penetrated by the piercing member, to a third position whereone or more interconnects and one or more corresponding contacts arepermitted to transmit a signal to the user. The interconnect(s) and thecorresponding contact(s) are configured such that, for example: (a) theinterconnect(s) or the contact(s) is positioned upon an aspect of thedrive mechanism and the other is positioned within or at least partiallyproximal to the plunger seal, to transmit a signal to the user when theplunger seal and the pierceable seal are substantially in contact; (b)the interconnect(s) or the contact(s) is positioned within or at leastpartially distal to the pierceable seal and the other is positionedproximal to the connector hub, to transmit a signal to the user when theplunger seal and the pierceable seal are substantially in contact; (c)the interconnect(s) and the contact(s) are situated within the sterilecavity between the connector hub and the pierceable seal, such after theseal is pierced, continued pressure within the drug chamber causesinterconnection which transmits a signal to the user, which signal isterminated once pressure inside the drug chamber drops andinterconnection is lost, i.e., at end of dose. A number of knowninterconnects and contacts may be utilized within the embodiments of thepresent disclosure, which would readily be appreciated by an ordinarilyskilled artisan. For example, a range of: Hall effect sensors; giantmagneto resistance (GMR) or magnetic field sensors; optical sensors;capacitive or capacitance change sensors; ultrasonic sensors; and lineartravel, LVDT, linear resistive, or radiometric linear resistive sensors;and combinations thereof, which are capable of coordinating to transmita signal to the user may be utilized for such purposes.

Additionally, the fluid pathway connectors may include one or more flowrestrictors. In at least one embodiment, the connector hub may at leastpartially function as a fluid conduit or flow restrictor. In at leastone embodiment, the fluid pathway connector further includes a filter. Anumber of known filters can be utilized within the embodiments of thepresent disclosure, which would readily be appreciated by an ordinarilyskilled artisan. For example the filter may be a permeable membrane,semi-permeable membrane, or porous membrane, which encloses the sterilecavity from the outside environment.

The novel devices of the present embodiments provide container fluidpathway connectors that maintain the sterility of the fluid pathway andthat are integrated into the fluid container, and drug delivery devicesthat incorporate such integrated sterile fluid pathway connectors tofluid containers. Because the fluid path is disconnected until fluiddelivery is desired by the operator, the sterility of the fluid pathwayconnector, the fluid container, the fluid, and the interior of thedevice as a whole is maintained. Furthermore, the novel configurationsof the fluid pathway connectors and drug delivery devices of the presentdisclosure maintain the sterility of the fluid path through operation ofthe device. Because the path that the fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe fluid container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent embodiments do not require terminal sterilization uponcompletion of assembly. A further benefit of the present embodiments isthat the components described herein are designed to be modular suchthat, for example, the fluid pathway connector and other components ofthe device may be integrated into a housing and readily interface tofunction as a drug delivery device.

A further embodiment provides a method of assembly of an integratedsterile fluid pathway connector and fluid container. The sterile fluidpathway connector may first be assembled and then attached, mounted,connected, or otherwise integrated into fluid container such that atleast a portion of the pierceable seal is contained within the drugcontainer. The fluid container can then be filled with a fluid fordelivery to the user and plugged with a plunger seal at an end oppositethe pierceable seal. The barrel can be filled with a fluid through theopen proximal end prior to insertion of the plunger seal from theproximal end of the barrel. A drive mechanism can then be attached tothe proximal end of the fluid container such that a component of thedrive mechanism is capable of contacting the plunger seal. An insertionmechanism can be assembled and attached to the other end of the fluidconduit. This entire sub-assembly, including drive mechanism, drugcontainer, fluid pathway connector, fluid conduit, and insertionmechanism can be sterilized, as described above, before assembly into adrug delivery device. Certain components of this sub-assembly may bemounted to an assembly platform within the housing or directly to theinterior of the housing, and other components may be mounted to a guide,channel, or other component or aspect for activation by the user. Amethod of manufacturing a drug delivery device includes the step ofattaching both the fluid pathway connector and fluid container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the drive mechanism, fluid container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described herein, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. In the instance in which the fluid is a drug, andthe drug delivery device is an ambulatory infusion device, an adhesivepatch and patch liner may be attached to the housing surface of the drugdelivery device that contacts the user during operation of the device.

A method of operating the drug delivery device includes one or more ofthe following steps: activating, by a user, the activation mechanism;displacing a control arm to actuate an insertion mechanism; activating adrive control mechanism to push the plunger seal, connect the sterilefluid pathway connector, and drive fluid flow through the drug deliverydevice; wherein the pushing of the plunger seal translates the fluid andthus causes a pierceable seal to deform in the direction of the fluidconduit and be pierced by a piercing member, to thereby open a fluidpath from the fluid container to the fluid conduit. The drive controlmechanism may be activated by actuating a power and control system. Themethod may further include the step of: engaging an optional on-bodysensor prior to activating the activation mechanism. Furthermore, themethod of operation may include translating a plunger seal within thedrive control mechanism and fluid container to force fluid flow throughthe fluid container, the fluid pathway connector, the fluid conduit, andthe insertion mechanism for delivery of the fluid to the desired target,e.g., to the body of a patient.

The novel devices of the present embodiments provide containerconnections which maintain the sterility of the fluid pathway and whichare integrated into the fluid container, and drug delivery devices whichincorporate such integrated sterile fluid pathway connectors to fluidcontainers. For example, such devices are safe and easy to use, and areaesthetically and ergonomically appealing for self-administeringpatients.

In at least one embodiment, the presently disclosed sterile fluidpathway connector includes a piercing member, a connector hub, and apierceable seal; wherein at least a portion of the pierceable seal isconfigured to move from a first position in which the piercing member isretained within a sterile cavity between the pierceable seal and theconnector hub, to a second position in which the pierceable seal hasbeen penetrated by the piercing member. A filter may be utilized toenclose the sterile cavity from the outside environment. Such fluidpathway connectors may be integrated into a fluid container having abarrel and a plunger seal. The components of the fluid pathway connectormay further be capable of transmitting a signal to the user uponcompletion of fluid delivery, for example, upon contact between theplunger seal and the pierceable seal. A fluid delivery pump includessuch integrated fluid pathway connectors and fluid containers.

The novel embodiments presented herein provide integrated sterile fluidpathway connectors and fluid containers, and drug delivery devices thatutilize such connections, configured to maintain the sterility of thefluid pathway before, during, and after operation of the device, andthat enable active safety controls for the device. Integration of thefluid pathway connector into a portion of the fluid container helpsensure container integrity and sterility of the fluid pathway.Additionally, by integrating the sterile fluid pathway connector into aportion of the fluid container, the connection for fluid transfer can becontrolled by the user (i.e., is user-activated) and enabled by thefunction of the drive mechanism. Accordingly, user-activation steps andthe internal operation of the drug delivery device can be greatlysimplified by the novel integrated sterile fluid pathway connectors ofthe present embodiments.

The novel embodiments provide container connections that maintain thesterility of the fluid pathway and are integrated into the fluidcontainer, and drug delivery devices that incorporate such integratedsterile fluid pathway connectors to fluid containers. The presentembodiments also further integrate the sterile pathway connector intothe fluid container, to reduce the necessary components or to provideeasier and more efficient operation of the connection and drug deliverydevices. The connector, the sterile fluid pathway assembly, and theinfusion pump disclosed here are not limited to medical applications,but may include any application, including industrial uses, wheresterile or uncontaminated fluid delivery may be desired. When the fluidis a drug, the present embodiments provide for devices that are safe andeasy to use, and are aesthetically and ergonomically appealing forself-administering patients. The embodiment described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. One or more of the components of thepresent embodiments may be modular in that they can be, for example,pre-assembled as separate components and configured into position withinthe housing of the drug delivery device during manufacturing.

FIG. 53A and FIG. 53B show an initial configuration of an embodiment ofa sterile fluid pathway connector 23030 integrated with fluid container23050 having fluid chamber 23021 and plunger seal 23060. In someembodiments, the fluid pathway connector 23030 and the fluid container23050 may be substituted, partially or entirely, for the fluid pathwayconnector 30 and the fluid container 50 illustrated in FIG. 1B of thepresent application. Fluid pathway connector 23030 may be mounted,connected or otherwise attached, permanently or removably, to fluidcontainer 23050 at an end opposite plunger seal 23060. As shown in theembodiment of FIG. 53A and FIG. 53B, fluid container 23050 has mutablefluid chamber 23021 within barrel 23058, defined by the position ofpierceable seal 23056 and plunger seal 23060. The seals described hereincan be made of a number of materials, but are typically made of one ormore elastomers or rubbers. Fluid chamber 23021 may contain a fluid fordelivery through the integrated sterile fluid pathway connector 23030.In the embodiment of FIG. 53A and FIG. 53B, the fluid pathway connector23030 includes sterile fluid conduit 23035, piercing member 23033,connector hub 23031, and pierceable seal 23056. Fluid pathway connector23030 includes piercing member guide 37 engaged with connector hub23031, upon which pierceable seal 23056 may interface with piercingmember 23033 of connector hub 23031 during operation. A permeable,semi-permeable, or porous membrane, such as filter 23039, may be used toallow venting of air from within the fluid pathway connector 23030during operation of the device, such as through port or vent 23031B inconnector hub 23031. Filter 23039 may be attached, mounted, bonded,over-molded, co-molded, pre-formed, or otherwise connected to enclosesterile cavity 23032 between the exterior of connector hub 23031 andpierceable seal 23056. The term “enclose” or “enclosure” is used hereinto define at least a semi-permeable or porous confined area that iscapable of being sterilized, evacuated by vacuum, and vented, but is notpenetrable by microorganisms, contaminants, or other undesirableenvironmental factors. For example, filter 23039 can be over-molded atleast partially within connector hub 23031 to separate the sterilecavity 23032 from the outside environment. In some embodiments, thefilter is a membrane, e.g., a semi-permeable membrane, which allows theventing of air during the actuation of pierceable seal 23056, fluidpathway connector 23030, and the pump device. Filter 23039 may besterilized by methods well-known to one having skill in the art, thusthe filter can maintain a sterile barrier to prevent exposure of thepiercing member 23033 to microorganisms, contaminants, or otherundesirable environmental factors.

As shown in FIG. 53B, piercing member 23033 is retained within theintegrated sterile fluid pathway connector 23030, at or near sealbarrier 23056C of pierceable seal 23056. Piercing member 23033 may be anaspect of fluid conduit 23035 or may be a separate component from fluidconduit 23035, as would readily be appreciated by one having skill inthe art. Additionally, fluid pathway connector 23030 may optionallyinclude one or more gaskets, O-rings, or other sealing members,compressed to seal between barrel 23058, particularly at lip 23058A,connector hub 23031, and housing 23052. In at least one embodiment,sealing aspect 23056A of the pierceable seal 23056 may be configured asa seal between barrel lip 23058A, connector hub 23031, and housing23052. Housing 23052 may be a separate component, such as a crimp cap,or may be an aspect of connector hub 23031 capable of mounting to barrel23058. The housing or cap could also have screw threads configured tocomplement screw threads in a fluid container, or use other impermanentmeans for connecting the fluid container to the sterile fluid pathwayconnector. As shown in FIG. 53A and FIG. 53B, the sterile fluid pathwayconnector 23030 may be attached to (i.e., integrated with) fluidcontainer 23050; which in turn can be mounted, by a number of knownmethods, either fixedly or removably to an assembly platform or housingof a fluid pump, such as the drug delivery device 10 as shown in FIGS.1A-1C. The assembly platform may be a separate component from thehousing, or may be a unified component of the housing such as apre-formed mounting aspect on the interior surfaces of the housing. Insuch configurations, the sterility of the fluid pathway is maintained,the pathway for fluid flow is not connected until desired by the user,and user-initiated activation causes the connection of the fluid chamberand the fluid pathway connector. The fluid pathway connector may,optionally, further include one or more separate flow restrictors or oneor more of piercing member 23033 and fluid conduit 23035 mayadditionally function as flow restrictors.

The integrated fluid connection of the present embodiments is furtherillustrated with reference to a drive mechanism, as shown in FIG. 54Aand FIG. 54B. The embodiment comprises fluid conduit 23035, engaged withpiercing member 23033 at engagement 23038, connector hub 23031 thatincludes vent 23031B, filter 23039 which is housed against connector hub23031, and pierceable seal 23056, which sealing portion 23056A abutsconnector hub 23031 and the end of barrel 23058, all of which are housedin cap 23052. Barrel 23058 comprises mutable fluid chamber 23021, andhouses plunger seal 23060 which is slidably disposed therein and incontact with a drive mechanism (e.g., the drive mechanism 100illustrated in FIG. 1B), which includes biasing member 23099. FIG. 54Ais an exploded side view of components of an integrated sterile fluidpathway connector and fluid container according to at least oneembodiment. FIG. 54B shows a sectional exploded view of the sameembodiment. Sterile fluid pathway connector 23030 may be integrated atleast partially within fluid container 23050 at an end opposite ofplunger seal 23060. An exemplary drive mechanism 23090 is shown in thesefigures to clarify the orientation of these components. The componentsof the novel sterile fluid pathway connector 23030 may be pre-assembled(see, e.g., FIG. 56A) and subsequently attached, mounted, connected orotherwise mated, permanently or removably, with a fluid container suchas fluid container 23050.

A number of drive mechanisms may be utilized to force fluid from a fluidcontainer for delivery. In one such embodiment, the drive mechanism23090 may be substantially similar to that described in WO2013/023033467 (PCT/US2012/023052303241). The components of the drivemechanism upon activation, may be used to drive axial translation in thedistal direction (i.e., toward housing 23052 of FIG. 53) of the plungerseal of the fluid container. Optionally, the drive mechanism may includeone or more compliance features that enable additional axial translationof the plunger seal to ensure, for example, that substantially theentire drug dose has been delivered to the user and that the feedbackcontact mechanisms have connected or interconnected. Furthermore, thedrive mechanism may include one or more safety mechanisms, such aspremature activation prevention mechanisms, to enhance the safety andusability of the mechanism and the device.

In a particular embodiment, drive mechanism 23090 employs one or morecompression springs 23099 as biasing member(s), as shown in FIG. 54B.Upon activation of the fluid pump by the user, the power and controlsystem is actuated to directly or indirectly release the compressionspring(s) from an energized state. Upon release, the compressionspring(s) may bear against and act upon the plunger seal 23060 to forcethe fluid out of the mutable fluid chamber 23021 of drug container 23050as further described with reference to FIG. 55A-55C.

FIG. 55A to FIG. 55C illustrate the features of an embodiment beforeuse, upon piercing of the pierceable seal, and upon completion of fluiddelivery. More specifically, in the configuration shown in FIG. 55A,piercing member 23033 is maintained within sterile cavity 23032 with afirst end (a proximal end) adjacent to, or contacting, pierceable seal23056 of fluid pathway connector 23030. The sterility of cavity 23032and piercing member 23033 is maintained, for example, by filter 23039disposed between sterile cavity 23032 and the outside environment. In atleast one embodiment, as shown in FIG. 55, filter 23039 is connected to,engaged with, or part of connector hub 23031, and encloses sterilecavity 23032 from the outside environment. Sterile cavity 23032 can bevented via vent or port 23031B within hub connection 23031. Accordingly,fluid pathway connector 23030, in at least one embodiment, is mounted toand integrated with fluid container 23050, for example by housing (cap)23052 engaged with lip 23058A of barrel 23058. The piercing member maybe a number of cannulas or conduits, such as rigid needles, and may becomprised of a number of materials, such as steel. In at least oneembodiment, piercing member 23033 is a rigid steel needle. Pierceableseal 23056 may have sealing aspect 23056A that permits pierceable seal23056 to be mounted directly to or otherwise be held in position betweenbarrel 23058, connector hub 23031, and cap 23052. Connector hub 23031includes an internal seal mount 23034 that further stabilizes theposition of more stationary aspects of pierceable membrane 23056. Atleast a portion of pierceable seal 23056, such as seal barrier 23056C,is translatable upon connector hub 23031, as described herein, torupture against piercing member 23033 and enable the fluid pathwayconnector to sterile fluid conduit 23035. Advantageously, such anarrangement permits pierceable seal 23056 to translate towards cap 23052but not towards the plunger seal 23060. This is a desirable feature thatpermits the mutable fluid chamber 23021 of the fluid container 23050 tobe evacuated, such as by vacuum, prior to filling with a fluid withoutcompromising the function of sterile fluid pathway connector 23030.

In an initial position the proximal end of piercing member 23033 mayreside adjacent to, or in contact with, seal barrier 23056C ofpierceable seal 23056 to, for example, minimize the distance oftranslation of the seal barrier 23056C to become pierced and open fluidcontainer 23050 to fluid pathway connector 23030. In a particularembodiment, proximal end of the piercing member 23033 may reside atleast partially within seal barrier 23056C of pierceable seal 23056, yetnot fully passing there-through, until activation of the device by auser.

As shown in FIG. 55B, once the pump device is activated and the drivemechanism pushes plunger seal 23060, plunger seal 23060 asserts a forceon fluid chamber 23021, and pneumatic and/or hydraulic pressure buildsby compression of the fluid in chamber 23021. As pneumatic and/orhydraulic pressure builds within fluid chamber 23021, the force isrelayed to pierceable seal 23056, causing barrier seal 23056C totransform. This transformation may include a shift, inversion,translation, flexion, deformation, pop, snap, or any other functionallyequivalent change, such that a portion of pierceable seal 23056, such asseal barrier 23056C, impinges against the substantially fixed positionof piercing member 23033 and causes piercing member 23033 to piercepierceable seal 23056 at seal barrier 23056C, as shown in FIG. 55B,thereby opening or otherwise connecting the fluid pathway betweenmutable fluid chamber 23021, piercing member 23033, and fluid conduit23035.

Accordingly, integrated sterile fluid pathway connector 23030 isconnected (i.e., the fluid pathway is opened) by the pneumatic and/orhydraulic force of the fluid within the fluid chamber 23021 created byactivation of the drive mechanism. Once integrated sterile fluid pathwayconnector 23030 is connected or opened, fluid is permitted to flow fromthe fluid container 23050, through integrated sterile fluid pathwayconnector 23030 and sterile fluid conduit 23035. In aspects in which thefluid pump is an ambulatory drug infusion pump, fluid drug then flowsthrough the insertion mechanism and into the body of the user for drugdelivery. In at least one embodiment, a number of flow restrictors maybe optionally utilized to modify the flow of fluid within the fluidpathway connector. In at least one embodiment, the fluid flows throughonly a manifold and a cannula or needle of the insertion mechanism,thereby maintaining the sterility of the fluid pathway before and duringfluid delivery.

Additionally or alternatively, plunger seal 23060 or the pierceable seal23056 may have some compressibility permitting a compliance push offluid from drug container 23050. Additionally, the drive mechanism,plunger seal 23060, connector hub 23031, pierceable seal 23056, or acombination thereof, may include one or more sensors or statusindication mechanisms, such as interconnects and contacts, to measureand communicate the status of drug delivery drive before, during, andafter operation of the device to deliver fluid.

FIG. 55C shows the components of fluid container 23050 and sterile fluidpathway connector 23030 after substantially all of the fluid has beenpushed out of the fluid container 23050. In particular, plunger seal23060 is in the most-distal position in barrel 23058. In the embodimentof FIG. 55C, the connector hub-side (e.g., distal end) of plunger seal23060 is configured with an optional protrusion and cavity aspect 23069,which structure minimizes residual volume left in fluid chamber 23021,now collapsed. Alternatively, plunger seal may be a flat-faced plungerseal (e.g., plunger seal 23160 in FIG. 57A and FIG. 58), or may have anynumber of other configurations as would be readily appreciated by onehaving skill in the art. In the embodiment shown in FIG. 55, plungerseal 23060 further comprises interconnect/contact 23061; and connectorhub 23031 further comprises interconnect/contact 62. At end-of-delivery,interconnect/contact 61 of plunger seal 23060 and interconnect/contact62 of connector hub 23031 interconnect and transduce a signal that maybe perceived by a user. As described herein, numerous sensors and signaltransducing means can be incorporated or adapted for use in the presentembodiments.

Because of the novel design of the fluid pathway connector of thepresent embodiments and their integration at least partially withinfluid containers, sterility of the fluid pathway is maintainedthroughout transport, storage, and operation of the device;user-activation of the device is simplified; and the fluid pathway isonly connected when desired by the user. The sterility of the fluidpathway connector is initially maintained by performing the connectionwithin a sterile cavity 23032 between connector hub 23031, pierceableseal 23056, and piercing member guide 23037. In at least one embodiment,the sterility of cavity 23032 is maintained by filter 23039 that abuts,is engaged with or part of, connector hub 23031. Filter 23039 may be,for example, a semi-permeable membrane that allows the venting of airthrough vent 23031B of connector hub 23031 during the actuation andtranslation of pierceable seal 23056. Filter 23039 may be sterilized bytypical sterilization methods, which would readily be appreciated by onehaving skill in the art, and may be used to maintain a sterile barrierthat prevents exposing piercing member 23033 to microorganisms,contaminants, or other undesirable environmental factors. For example,upon substantially simultaneous activation of the insertion mechanism,the fluid pathway between mutable fluid chamber 23021 and insertionmechanism is complete to permit drug delivery into the body of the user.Because fluid pathway connector 23030 is not in fluid connection orcommunication with fluid chamber 23021 until activation of the fluidpump and drive mechanism, fluid flow from the fluid container 23050 isprevented until desired by the user. This provides an important safetyfeature to the user and also maintains the container integrity of thefluid container and sterility of the fluid pathway.

The drive mechanism that translates the plunger seal 23060 may containone or more drive biasing members (e.g., as shown in FIG. 54B). Thecomponents of the drive mechanism function to force a fluid from themutable fluid chamber 23021 through pierceable seal 23056 and throughthe piercing member 23033 or sterile fluid conduit 23035, for deliverythrough fluid pathway connector 23030. Further regarding the drivemechanism, a number of drive mechanisms may be utilized to force fluidfrom a drug container for delivery into the body of a user. In one suchembodiment, the drive mechanism 23090 may be substantially similar tothat described in WO 2013/023033467 (PCT/US2012/023052303241), which ishereby incorporated by reference in its entirety. The components of thedrive mechanism, upon activation, drive axial translation in the distaldirection of the plunger seal of the drug container. Optionally, drivemechanism may include one or more compliance features which enableadditional axial translation of the plunger seal to, for example, ensurethat substantially the entire fluid dose has been delivered to the userand make sure that the feedback contact mechanisms have connected.Furthermore, the drive mechanism may include one or more safetymechanisms, such as premature activation prevention mechanisms, toenhance the safety and usability of the mechanism and the device.

At least one embodiment provides for a modular fluid pathway connector.FIG. 56A and FIG. 56B detail an embodiment of a modular fluid pathwayconnector that comprises connector hub 23031, which abuts filter 23039and pierceable seal 23056 at sealing member 23056A. Connector hub 23031,filter 23039 and pierceable seal 23056 are housed within cap 23052, asshown in FIG. 56A. Connector hub 23031 further comprises header 23031C,which forms a junction for fluid conduit 23035 and piercing member23033. As shown in FIG. 56A and FIG. 56B, fluid conduit 23035 may beconnected directly to piercing member 23033. Alternatively, as shown inFIG. 57A fluid conduit 223035 may be connected via conduit port 223038.Nevertheless, a modular fluid pathway connector can be adapted for usewith a number of alternative barrel and drive configurations, and usedwithin a variety of ambulatory infusion devices. The components of thenovel sterile fluid pathway connector 23030 may be pre-assembled, toappear as exemplified in FIG. 56A, and subsequently attached, mounted,connected, or otherwise mated with a fluid container such as fluidcontainer 23050. Alternatively, the components of sterile fluid pathwayconnector 23030 may be assembled directly into drug container 23050. Aswould be readily appreciated by one skilled in the art, a number ofglues or adhesives, or other connection methods such as snap-fit,interference fit, screw fit, fusion joining, welding, ultrasonicwelding, laser welding, and mechanical fastening, and the like, can beused to engage one or more of the components described herein inpermanent or impermanent connection as desired for a particular use. Forexample, glue can be used between distal end of barrel 23058, sealingmember 23056A, or connector hub 23031A. Additionally or alternatively,the components of the sterile fluid pathway connector 23030 may bemounted to barrel 23058 and held in place crimping cap 23052 to distalaspect of barrel 23058, such as to a flanged aspect or lip of barrel23058A.

In at least one embodiment, as shown in FIG. 57A to FIG. 57C, piercingmember guide 230237 may be utilized to guide pierceable seal 23056 andto slidably engage the connector hub 230231. Additionally oralternatively, piercing member guide 230237 may be utilized to ensurethat piercing member 230233 remains substantially centered on the axisso as to pierce pierceable seal 23056 at the desired portion of sealbarrier 23056C. The embodiment of FIG. 57A shows fluid containercomprising barrel 23058 and forming mutable fluid chamber 23021 betweenplunger seal 230260 and pierceable seal 56. As shown in FIG. 57A,plunger seal 230260 is a flat plunger seal, but a variety of plungerseal shapes can be adapted for use with the fluid connection andinfusion pumps of the present embodiments. The embodiment of FIG. 57Afurther comprises filter 23039, which abuts connector hub 230231 and isused to maintain sterility of sterile chamber 23032 between connectorhub 230231 and pierceable seal 23056. Connector hub 230231 also includesseal mount 230234 that abuts pierceable seal 23056; and flange 230231Athat abuts seal member 23056A of seal 23056, and that, in turn, abutsthe distal lip 23058A of barrel 23058. The meeting surfaces of connectorhub 230231A, sealing member 23056A and barrel lip 23058A are positionedin place and secured within the rims of cap 23052. Connector hub 230231also houses piercing member 230233, which connects to fluid conduit230235. Connector hub 230231 also has vacuum port 230231B, a filteredchannel that leads into sterile chamber 23032. Connector hub 230231 isalso configured with conduit port 230231D, which provides exit fromsterile fluid connector 230230 to the rest of the infusion device (e.g.,injection means), such as via sterile fluid conduit 23035 (not shown).Conduit port 230231D and vacuum port 230231B may contain a membrane orseals, such as one-way seals, which permit fluid flow out of chamber23032 through the respective ports but do not permit fluid flow into thechamber 23032 through these ports. Additionally, or alternatively,conduit port 230231D and vacuum port 230231B may be plugged at certainpoints of assembly or operation. For example, vacuum port 230231B may beused to evacuate sterile cavity 23032 during manufacturing, assembly, orat any point prior to operation of the device; and then vacuum port230231B can be plugged after the evacuation has been completed.

Further regarding piercing member guide 230237, this component may beslidably attached to connector hub 230231. A number of means known inthe art may be used to facilitate this slidable attachment such as, forexample, engagement between a connector prong 230237D and leg 230237A ofpiercing member guide 230237 with complementary cavity 230236 inconnector hub 230231. These components are more clearly visible in FIG.57A and FIG. 144B. FIG. 57B shows the orientation of piercing member230233 within piercing member guide 230237, which emerges from piercingmember guide 230237 at header 230237C; and FIG. 57C shows theorientation of piercing member 23033 and piercing member guide 230237within connector hub 230231. Such an arrangement permits the pierceableseal 23056 and piercing member guide 230237 to translate towards housing23052 together, at least for a portion of the translation of sealbarrier 23056C. Additionally, pierceable seal 23056 may be removablyattached to piercing member guide 230237 by a number of means known inthe art such as, for example, removable snap-fit engagement or it may beconfigured to enable contact between the components to guide thetranslation of the seal barrier 23056C upon the piercing member 230233.When a piercing member guide is used, such as piercing member guide230237 in FIG. 57A, the piercing member guide may translate withpierceable seal 23056, for at least a portion of the translation, toensure that the seal barrier 23056C contacts and is pierced by thepiercing member 230233. Once the fluid pathway is opened or connected,translation of plunger seal 230160 in the distal direction by the drivemechanism causes fluid within drug chamber 23021 to be forced throughthe sterile fluid connector. In some embodiments, a needle insertionmechanism, as described herein, may be connected at the other end of thefluid conduit 23035 to insert a needle into the body of the user tofacilitate fluid transfer to the user.

The embodiment shown in FIG. 57A also comprises plunger seal 260, whichmay be used as a part of the status indication mechanism along withpiercing member guide 237. More specifically, in this embodiment plungerseal 260 includes interconnect/contact 261 and the correspondinginterconnect/contact 262 is located on piercing member guide 237. Whenplunger seal 260 and piercing member guide 237 reach proximity atend-of-delivery (e.g., as in FIG. 57C), interconnect/contact 261 andinterconnect/contact 261 interconnect and transduce a perceptible signalto the user.

The novel embodiments presented herein provide integrated sterile fluidpathway connectors and fluid containers, and fluid pumps that utilizesuch connections, that are configured to maintain the sterility of thefluid pathway before, during, and after operation of the device, andthat enable active safety controls for the device. Integration of thefluid pathway connector into a portion of the fluid container helpsensure container integrity and sterility of the fluid pathway.Additionally, by integrating the sterile fluid pathway connector into aportion of the fluid container, the connection for fluid transfer can becontrolled by the user (i.e., user-activated) and enabled by thefunction of the drive mechanism. Accordingly, user-activation steps andthe internal operation of the fluid pump can be greatly simplified bythe novel integrated sterile fluid pathway connectors of the presentembodiments.

In another embodiment, the fluid container comprises at least twomutable internal compartments, wherein each compartment-compartmentinterface comprises a distinct pierceable seal capable of beingdisrupted by the piercing member of the sterile fluid pathway connectorto create a sterile fluid communication between the sterile fluidpathway and that compartment of the sterile fluid container. As shown inFIG. 58, container 23050 may utilize one or more seals in addition toplunger seal 230160 and pierceable seal 230156. This may be applicable,for example, when multiple fluid substances are desired to be deliveredby the container and the infusion pump device. FIG. 58 shows one suchembodiment that utilizes two additional seals, 230163 and 230165, tocreate compartments or chambers 230121A, 230121B and 230121C, withinwhich one or more fluid substances may be stored for delivery. Theembodiment of FIG. 58, pierceable seal 230156 includes seal barrier230156C and base 230156A, which base 230156A abuts barrel lip 23058A onits distal side and connector hub 230131A on its proximal side, whichabutments are held within housing 23052. Connector hub 230151 furtherincludes vacuum port 230131B, with a channel that leads into sterilechamber 23032. Connector hub 230131 is also configured with conduit port230131D, which provides exit from sterile fluid connector 230130 to therest of the infusion device (e.g., an injection mechanism). Conduit port230131D and vacuum port 230131B may each contain a membrane, filter orseals, such as one-way seals, which permit fluid flow out of chamber23032 through the respective ports but do not permit fluid flow into thechamber 23032 through said ports. Additionally, or alternatively,conduit port 230131D and vacuum port 230131B may be plugged at certainpoints of assembly or operation. For example, vacuum port 230131B may beused to evacuate sterile cavity 32 during manufacturing, assembly, or atany point prior to operation of the device; and then vacuum port 230131Bcan be plugged after the evacuation has been completed.

Upon activation of the fluid pump, pressure at interface 230168 ofplunger seal 230160 causes distal translation of plunger seal 230160towards housing 23052. The pneumatic and/or hydraulic pressure withinthe fluid substance(s) held in drug chambers 230121A, 230121B and230121C relays the force to, and causes distal translation of, chamberseal 230163, chamber seal 230165, and pierceable seal 230156, causingseal barrier 230156C to translate towards housing 23052 and becomepierced by piercing member 230133. This causes the sterile fluid pathwayconnector to be made or opened, as described herein. Upon furthertranslation of plunger seal 160, the fluid substance held in mutabledrug chamber 230121A is dispensed through conduit 230135. Upon furthertranslation of the fluids and seals, seal 230165 may be then be piercedby piercing member 230133, thereby permitting the fluid substance inmutable fluid chamber 230121B to be dispensed from the fluid pathwayconnector. If further compartments or chambers are desired, more sealsand chambers (such as seal 230163 and mutable chamber 230121C) may beconfigured, and subsequently engaged in the same manner until plungerseal 230160 has been fully translated towards housing 23052. Thisconfiguration may offer advantages over single-compartment fluidcontainers. For example, a diluent may be stored in mutable fluidchamber 230121A and a therapeutic drug may be stored in mutable fluidchamber 230121B, such that the sterile fluid pathway is first purged bythe diluent prior to delivery of the drug therapy to the patient. Whendrug combinations are desired for delivery, multiple therapeutic agentsmay be stored and delivered using the configuration provided by thisembodiment. Any number of seals and drug chambers may be utilized insuch a configuration provided that the piercing member 230133, the drivemechanism, and other components of the embodiments are configuredappropriately for such delivery.

The novel integrated sterile fluid pathway connectors of the presentdisclosure may additionally incorporate status indication into the fluiddelivery mechanisms. Such status indication features may be incorporatedinto the drive mechanism 23090, as described in WO 2013033467.Additionally or alternatively, status indication features may beincorporated into the components of the sterile fluid pathwayconnectors. In one embodiment, one or more interconnects are containedwithin, or proximal of, the plunger seal. At the end of fluid delivery,the piercing member may be utilized to contact the, or as a contact for,interconnect to open, close, or otherwise create a signal to the powerand control system to provide feedback to the user. In anotherembodiment, one of either interconnects/contacts are contained within,or proximal of the plunger seal, while the other is contained within ordistal of the pierceable seal, such as in or on a seal mount or guidepiece. At the end of fluid delivery, interconnects and correspondingcontacts are close enough to permit a signal to be sent to the power andcontrol system to provide feedback to the user.

In another embodiment, the surface of the connector hub sequestered insterile chamber 23032 may incorporate, or itself be utilized as, acontact or interconnect for the status indication mechanism. Forexample, an end-of-delivery signal can be provided using a leaf/flex armor spring style switch mechanism contained within sterile compartment23032, engaged with the surface of the connector hub and connectedthrough the hub to the appropriate electronics. In this arrangement, inthe unpressurized state (before device activation), the switch rests inthe open position, and there is no contact/interconnect or signaltransduced. When the device is activated, i.e., when the drive engagesthe plunger seal within the drug container, pneumatic and/or hydraulicpressure causes the pierceable seal to translate into the piecingmember, thus disrupting the pierceable seal and allowing fluid to flowthrough the sterile fluid connector. Pneumatic and/or hydraulic pressurefurther causes the septum of the pierceable seal to press against theswitch mechanism until it interconnects with its complementary contacts,which closes the circuit and allows a signal to transduce to the user,indicating that drug delivery has started. At end-of-delivery, thepneumatic and/or hydraulic pressure within the sterile chamber isreleased and the switch re-opens, breaking the circuit and providing anend-of-delivery signal to the user.

Such a configuration, in which the surface of the connector hubsequestered in the sterile chamber of the sterile fluid pathwayconnector may incorporate, or itself be utilized as, a contact orinterconnect for the status indication mechanism, may be facilitated bya configuration of the pierceable seal. For example, as shown in FIG.59A to FIG. 59E, fluid chamber 23058 comprises plunger seal 230160,configured to engage a drive mechanism that forces plunger seal 230160towards sterile fluid connector 230130. In the initial position (i.e.,before the drive is engaged), pierceable seal 230356 maintains sterilechamber 23032 within the space defined by pierceable seal 230356 andconnector hub 230131, particularly as partially maintained by seal mount230134, as shown in FIG. 59A. Connector hub 230131 further includespiercing member 23033, and vacuum port or vent 131B in which sterilityof chamber 23032 is maintained by filter 23039. Connector hub base230131A, sealing member 230356A of pierceable member 230356, and barrellip 23058A are all secured in housing 23052, which housing can be a capsuch as a crimp cap. Connector hub 230131 also includes exit port230131D, which provides an exit passage for fluid conduit 23035 from thesterile fluid pathway connector. Once a pump drive is activated andplunger seal 230160 is forced toward piercing member 23033, pneumaticand/or hydraulic pressure within mutable fluid chamber 23021 forces sealbarrier 230356C of pierceable seal 230356 into piercing member 23033,which pierces seal barrier 230356C and opens the sterile fluid pathway.Continued pneumatic and/or hydraulic pressure within mutable chamber23021 forces at least a portion of pierceable seal 230356 to contact atleast a portion of connector hub 230131 within sterile chamber 23032, asshown in FIG. 59B. This continued pneumatic and/or hydraulic pressure,as long as the drive is activated and fluid remains in mutable chamber23021, maintains the contact between seal 230356 and connector hub230131, as shown in FIGS. 59C and 59D. When fluid has been pumped out ofmutable fluid chamber 23021, such that this chamber essentially nolonger exists, pneumatic and/or hydraulic pressure against seal 230356is released, and seal 230356 returns to a non-pressurized state withinchamber 23032, in which there is no longer contact between seal 230356and hub 230131, as shown in FIG. 59E.

This aspect of the embodiments is advantageous for a number of devicesand configurations useful to provide the sterile fluid pathway connectorwith at least one sensor configured to indicate the status of fluidtransfer from the sterile fluid container to the connector. An exampleof such a sensor is a “switch” mechanism contained within the sterilechamber in the sterile fluid connector. For example, in the embodimentshown in FIG. 60A to FIG. 60H, fluid container 230350 includes barrel230358, which houses fluid chamber 230321 and plunger seal 230360,configured to engage a drive mechanism that forces plunger seal 230360and fluid in mutable fluid chamber 230321 toward sterile fluid connector230330. Pierceable seal 230356 maintains sterile chamber 230332 withinthe space defined by pierceable seal 230356 and connector hub 230331, asshown in FIG. 60A and FIG. 60B, in which the fluid pathway is “closed.”Connector 230330 further includes connector hub 230331, which furthervacuum port 230331B, in which sterility of chamber 230332 is maintainedby filter 230339; exit port 230331D, which provides an exit passage forfluid conduit 230335 from sterile fluid pathway connector 230330; andengages piercing member 333. Connector hub base 230331A, pierceable seal230356 sealing member 230356A, and barrel lip 230358A are secured inhousing 230352. Connector hub 230331 further houses, in sterile chamber230332, stamped ring 230391 fitted on seal mount 230334 of connector hub230331; contact 230392; spring 230393; and interconnects 230362 whichare in communication with flexible power strip 230394 (flex). As shownin FIG. 60A and FIG. 60B, in the initial state before activation of thedrive, spring 230393 rests in a non-compressed state, and contact 230392is held between spring 230393 and stamped ring 230391 in a position inwhich there is no contact between interconnects 230362 and contact230392. Contact 230392 is further stabilized within sterile chamber230332 by the position of piercing member 230333 that passes throughcontact 230392 through passage 230392C.

As shown in FIG. 60C and FIG. 60D, once the drive mechanism is activatedand plunger seal 230360 is forced toward piercing member 230333, asindicated by the arrow, pneumatic and/or hydraulic pressure withinmutable fluid chamber 230321 forces seal barrier 230356C of pierceableseal 230356 into piercing member 230333, thereby piercing seal barrier230356C and opening the sterile fluid pathway such that fluid can passto sterile fluid conduit 230335. This pneumatic and/or hydraulicpressure within mutable chamber 230321 also forces at least a portion ofbarrier seal 230356C against at least a portion of contact 230392, suchthat spring 230393 is compressed until contact 230392 meets withinterconnects 230362 within sterile chamber 230332, forming aninterconnection. A signal can then be transduced via contact 230392,interconnect 230362, and flex 230394. Continued pneumatic and/orhydraulic pressure (see arrow), as long as the drive is activated andfluid remains in mutable chamber 230321, compresses spring 230393 andmaintains the contact between seal 230356, contact 230392 andinterconnect 230362, such that interconnection continues, as shown inFIG. 60E to FIG. 60F. When fluid has been pumped out of mutable fluidchamber 230321, such that this chamber essentially no longer exists andflow through the sterile fluid connector 230330 has ceased, as shown inFIG. 60G and FIG. 60H (the latter is a different sectional view of thesterile fluid pathway connector showing the position of interconnects230362 within connector hub 230331), pneumatic and/or hydraulic pressureagainst seal 230356 is released, and spring 230393 returns to thenon-compressed state, pushing contact 230362 back toward stamped ring230391 and breaking interconnection between contact 230392 andinterconnect 230362. Once this interconnection is broken, signal can nolonger be transduced via flex 230394.

Other switch mechanisms can be designed that use the position of themembrane in pressured and unpressurized states to facilitatetransduction of a signal to indicate the status of fluid transfer fromthe sterile fluid container to the connector. For example, as shown inFIG. 61A to FIG. 61G, connector hub 230331 can house components of aswitch comprising a leaf/flex arm contacts 395. FIG. 61B, FIG. 61D andFIG. 61E show the sterile fluid pathway connector in the pre-useposition, in which pierceable seal 230356 is unpierced and intact. Inthis position, contacts 230395 are not touching (or in close enoughproximity with) interconnects 230362, and no signal can be transduced.FIG. 61C, FIG. 61F and FIG. 61G show the sterile fluid pathway connectorin the activated, pressurized position, in which pneumatic and/orhydraulic pressure from the fluid chamber has deformed barrier seal230356C against piercing member 230333, piercing pierceable seal 230356and opening the fluid pathway. In this position, barrier seal 230356Chas further been forced against contacts 230395, such that contacts230395 meet (or become in close enough proximity) with interconnects230362, such that interconnection forms a signal that can be transducedvia flex 230394. FIGS. 148D and 10F are perspectives (in which thebarrel and housing are not shown), that illustrate the positions ofpierceable seal 230356, connector hub 230331, and piercing member 230333in pre-use and pressurized positions, respectively. FIGS. 61E and 61Gare perspectives in which the barrel, housing and pierceable seal arenot shown, to illustrate the positions of contacts 230395 andinterconnects 230362 in pre-use (no interconnection) and pressurized(interconnected) positions, respectively.

FIG. 62A to FIG. 62D further illustrate an embodiment in which leaf/armcontacts 230395 do not form interconnection with interconnects 362 untiland unless, as shown in FIG. 62B and FIG. 62D, pneumatic and/orhydraulic pressure force seal barrier 230356C onto connects 230395,which force then transferred to place contacts 230395 in contact withinterconnects 230362, which then allows signal flow via flex 230394.Additionally, as shown in the embodiment of FIG. 62A to FIG. 62D,connector hub 230331 further includes internal post 230334A, a structurethat limits position of contacts 230395 and membrane 230356 to avoid anover-center position that might interfere with fluid passage through thesterile fluid pathway connector.

FIG. 63A to FIG. 63D further illustrate an embodiment of a sterile fluidconnector capable of transmitting a signal indicating the status offluid transfer from the sterile fluid container to the connector. FIG.63B illustrates the position of components of a sterile fluid connector230330 in an unpressurized state, while FIG. 63C illustrates thepressurized state and FIG. 63D illustrates an end-of-delivery state.Interconnect(s) 230362 and contact(s) 230395 are situated within sterilechamber 230332 between connector hub 230331 and pierceable seal 230356,such that after pierceable seal 230356 is pierced, continued pressurewithin drug chamber 230321 causes interconnection between one or moreinterconnect(s) 230362 and one or more contact(s) 230395, whichtransmits a signal to the user, and which signal is terminated oncepressure inside the drug chamber 321 drops and interconnection is lost,i.e., at end-of-delivery. A number of known interconnects and contactsmay be used with the present embodiments, which would readily beappreciated by a skilled artisan. For example, a range of: Hall effectsensors; giant magneto resistance (GMR) or magnetic field sensors;optical sensors; capacitive or capacitance change sensors; ultrasonicsensors; and linear travel, LVDT, linear resistive, or radiometriclinear resistive sensors; and combinations thereof, which are capable ofcoordinating to transmit a signal to the user may be utilized for suchpurposes. FIG. 64A to FIG. 64C illustrate another embodiment of asterile fluid connector capable of transmitting a signal indicating thestatus of fluid transfer from the sterile fluid container to theconnector.

Yet another switch mechanism is shown in FIG. 65A and FIG. 65B, whichshow sectional and sectional isometric views of a sterile fluid pathwayconnector (barrel not shown). In this embodiment, sterile chamber230332, defined in part by the position of pierceable seal 230356 sealmount 230334 and hub connection 230331. Connector hub also holdspiercing member 230333 and interconnects 230362 within the sterilechamber 230332. The switch mechanism includes interconnects 230362,first compression spring 230393, contact 230392, and second compressionspring 230396. In this embodiment, shown in the un-activated,depressurized state, both compression springs 230393 and 396 compress inorder for contact 230392 to form an interconnection with interconnects230362. Before and upon release of pneumatic and/or hydraulic pressureagainst seal barrier 230356, compression springs 230393 and 230396decompress and interconnection is broken.

Another embodiment of a switch mechanism is shown in FIG. 66A and FIG.66B. In this embodiment, pierceable seal 230456 comprises a conductivematerial or coating. Connector hub 230431 includes rib 434A, a structurethat ensures that continuity between conductive pierceable seal 230456and contacts 230462 is broken when system pressure drops at the end offluid delivery. More specifically, as shown in FIG. 66B, in thepressurized system in which pneumatic and/or hydraulic pressure hascaused conductive pierceable membrane 230456 to have been ruptured bypiercing member 230433, conductive pierceable membrane 230456 mustdeform further proximal to rib 230434 in order to meet interconnects230462. Once pneumatic and/or hydraulic pressure ceases, i.e., at theend of fluid delivery, conductive pierceable membrane 230456 isnaturally released from interconnection by proximal to rib 230434

Yet another embodiment of a switch mechanism is shown in FIG. 67. Inthis embodiment, connector hub 230531 comprises conductive elastomer230597 held in sterile chamber 230532 between connector hub 230531 andpierceable membrane 230556. In this embodiment, at least a portion ofconductive elastomer 230597 is affixed to or otherwise engaged with sealmount 230534, and is configured with a centrally located aperture toallow barrier seal 230556C to be forced into contact with piercingmember 230533 upon activation of the pump and creation of pneumaticand/or hydraulic pressure against pierceable membrane 230556. Conductiveelastomer 230597 is “springy” in nature and can deform (i.e., stretch)in response to distal force from pierceable seal 230556, therebydeformed into meeting interconnects 230362 under pressure frompierceable seal 230356. The elastomeric nature of conductive elastomer230597 allows it to return to the pre-deformed state, in which there isno interconnection, in an unpressurized environment. Therefore, oncepneumatic and/or hydraulic pressure ceases, i.e., at end-of-delivery,conductive elastomer film 230597 is passively released from contact withinterconnections 230562, and signal is interrupted.

In another embodiment, shown in FIG. 68, the sterile fluid pathwayconnector includes a sensor mechanism comprising dome switch 230666,which dome is made or of includes conductive material such that domeswitch 230666 can act as a contact to create a signal when dome switch230666 meets with, or moves sufficiently close to, interconnects 230662to complete the circuit. Dome switch 230666 is configured with at leastone outer portion 230666A that resists deformation and engages with orbears against the inner wall of connector hub seal mount 230634.Alternatively, the outer deformation-resistant portion of the domeswitch can be a radial ring, or any structure that will stabilize theposition of the dome within the sterile fluid pathway connector. Theconductive portion of the dome switch may comprise shape-memory alloythat “remembers” its dome shape, but can be deformed into a moreflattened shape under pressure, then return to the dome shape oncepressure is relieved. In the embodiment of FIG. 68, dome switch 230666further comprises aperture 230666C through which piercing member 230633can pass as dome switch 230666 is pressed in the direction ofinterconnects 230662. More specifically, when the pump device isactuated and pneumatic and/or hydraulic pressure builds against thepierceable membrane (not shown), the pierceable membrane is forced ontopiercing member 230633 and ruptured to open the fluid pathway. Domeswitch 230666 is similarly deformed by the pneumatic and/or hydraulicpressure or by the distal pressure of the deformed portion of thepierceable seal bearing against it, and dome switch 666 flattens towardsinterconnects 230662 to allow a signal to be transduced. Once thepneumatic and/or hydraulic pressure stops, i.e., at end-of-delivery, thedome switch returns to its pre-deformed dome shape and interconnectionceases. As shown in FIG. 68, dome switch 230666 is configured forplacement under the pierceable seal (not shown), within the sterilecavity of the fluid pathway connector. The dome switch could, however,be configured to “ride” on top of the pierceable seal, and uponpressurization would be pushed in close enough proximity withinterconnects 230662 to generate a signal. Alternatively, the domeswitch could be made of evenly deformable/resistant shape-memorymaterial with the conductive portion of the dome switch configured inthe outer portions or rim of the dome, and be placed “upside down” (as abowl shape) in the sterile chamber of the fluid pathway connector. Inthis configuration, the pneumatic and/or hydraulic pressure against thepierced pierceable membrane would sufficiently flatten the dome untilthe outer conductive part of the dome made sufficient contact withinterconnects positioned in the connector hub to allow a signal. Uponcessation of pressure, i.e., at end-of-delivery, the dome would pop backto its remembered dome shape, and thereby remove the connective contactsfrom interconnection.

As should be clear from the preceding discussions, a number of knowninterconnects and contacts, or similar components, are known in the artand may be utilized within the novel embodiments disclosed herein. Aswould readily be appreciated by one having skill in the art, a vastrange of magnets, sensors, coils, and the like may be utilized toconnect, transmit, or relay a signal for user feedback. Generally, anyRLC circuit systems having a resistor, an inductor, and a capacitor,connected in series or in parallel, may be utilized for this purpose.For example, Hall effect sensors; giant magneto resistance (GMR) ormagnetic field sensors; optical sensors; capacitive or capacitancechange sensors; ultrasonic sensors; or linear travel, LVDT, linearresistive, or radiometric linear resistive sensors may be utilized asinterconnects and corresponding contacts used to permit a signal to besent to the power and control system to provide feedback to the user.The location of the contacts and interconnects may be interchanged or ina number of other configurations which permit completion of anelectrical circuit or otherwise permit a transmission between thecomponents. By use of one or more status switch interconnects and one ormore corresponding electrical contacts, the status of the drivemechanism before, during, and after operation can be relayed to thepower and control system to provide feedback to the user. Such feedbackmay be tactile, visual or auditory, and may be redundant such that morethan one signals or types of feedback are provided to the user duringuse of the device.

Additionally, the embodiments of the present disclosure provideend-of-delivery compliance to ensure that substantially the entire fluidvolume has been delivered and that the status indication features havebeen properly contacted to provide accurate feedback to the user.Through these mechanisms, confirmation of fluid delivery can accuratelybe provided to the user or administrator. Accordingly, the novel devicesof the present disclosure alleviate one or more of the problemsassociated with prior art devices. Optionally, the drive mechanism mayinclude one or more compliance features that enable additional axialtranslation of the plunger seal to, for example, ensure thatsubstantially the entire fluid volume has been delivered and make surethat the feedback contact mechanisms have connected. For example, in oneembodiment of the present disclosure, the drive mechanism may beconfigured to drive further axial translation of at least a portion ofthe plunger seal for a compliance push of the plunger seal, or of fluid,from the fluid container. Additionally or alternatively, the plungerseal, itself, may have some compressibility permitting a compliancepush. For example, when a pop-out plunger seal is employed, i.e., aplunger seal that is deformable from an initial state, the plunger sealmay be caused to deform or “pop-out” to provide a compliance push.Similarly, the plunger seal may be porous, compressible, deformable, orthe like to itself be capable of providing a compliance push.

As described above, the location of the contacts and interconnects maybe interchanged or in a number of other configurations that permitcompletion of an electrical circuit or otherwise permit a transmissionbetween the components. In one embodiment, the plunger seal mayincorporate, or itself be utilized as, a contact or interconnect for thestatus indication mechanism (e.g., 23061 in FIG. 55C). In oneembodiment, the seal mount may incorporate, or itself be utilized as, acontact or interconnect for the status indication mechanism (e.g., 23062in FIG. 55C). In one embodiment, a guide piece may incorporate, oritself be utilized as, a contact or interconnect for the statusindication mechanism (e.g., 230232 in FIG. 57A). In another embodiment,the proximal surface of the connector hub sequestered in sterile chamber32 may incorporate, or itself be utilized as, a contact or interconnectfor the status indication mechanism (e.g., FIG. 60 to FIG. 68).

Other components of the sterile fluid pathway connector may similarly beutilized for multiple functions. Alternatively, other optionalcomponents may be utilized within the novel embodiments of the presentdisclosure. For example, one or more optional flow restrictors may beutilized within the configurations of the fluid pathway connectordescribed herein. In at least one embodiment, a flow restrictor may beutilized at the connection between the piercing member and the fluidconduit. The fluid pump is capable of delivering a range of fluid withdifferent viscosities and volumes. The fluid pump is capable ofdelivering a fluid at a controlled flow rate (speed) or of a specifiedvolume. In one embodiment, the fluid delivery process is controlled byone or more flow restrictors within the fluid pathway connector and/orthe sterile fluid conduit. In other embodiments, other flow rates may beprovided by varying the geometry of the fluid flow path or deliveryconduit, varying the speed at which a component of the drive mechanismadvances into the fluid container to dispense the fluid therein, orcombinations thereof. In at least one embodiment of the presentdisclosure, the connector hub itself may be utilized as part of thefluid path and may, optionally, function as a flow restrictor.

It will be appreciated from the above description that the fluid pathwayconnectors and fluid pumps disclosed herein provide an efficient andeasily-operated system for automated fluid delivery from a fluidcontainer. The novel devices of the present disclosure provide containerconnections which maintain the sterility of the fluid pathway and whichare integrated into the fluid container, and fluid delivery pumps thatincorporate such integrated sterile fluid pathway connectors to fluidcontainers. Such devices are safe and easy to use, and are aestheticallyand ergonomically appealing for self-administering patients. The devicesdescribed herein incorporate features which make activation, operation,and lock-out of the device simple for even untrained users. Because thefluid path is disconnected until fluid delivery is desired by theoperator, the sterility of the fluid pathway connector, the fluidcontainer, the fluid, and the device as a whole is maintained. Theseaspects of the present embodiments provide highly desirable storage,transportation, and safety advantages to the operator. Furthermore, thenovel configurations of the fluid pathway connectors and drug pumps ofthe present disclosure maintain the sterility of the fluid path throughoperation of the device. Because the path that the fluid travels withinthe device is entirely maintained in a sterile condition, only thesecomponents need be sterilized during the manufacturing process. Suchcomponents include the fluid container of the drive mechanism, the fluidpathway connector, the sterile fluid conduit, and, when the fluid is adrug, the insertion mechanism. In at least one embodiment of the presentdisclosure, the power and control system, the assembly platform, thecontrol arm, the activation mechanism, the housing, and other componentsof the fluid pump do not need to be sterilized. This greatly improvesthe manufacturability of the device and reduces associated assemblycosts. Accordingly, the devices of the present disclosure do not requireterminal sterilization upon completion of assembly. A further benefit ofthe present embodiments is that the components described herein aredesigned to be modular such that, for example, the fluid pathwayconnector and other components of the device may be integrated into ahousing and readily interface to function as a fluid pump.

Assembly or manufacturing of fluid pathway connector 23030 or any of theindividual components may utilize a number of known materials andmethodologies in the art. For example, a number of known cleaning fluidssuch as isopropyl alcohol and hexane may be used to clean the componentsor the devices. A number of known adhesives may similarly be employed inthe manufacturing process. Additionally, known siliconization orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The fluid pathway connector may be assembled in a number ofmethodologies. In one method of assembly, the sterile fluid pathwayconnector may be assembled, e.g., as shown in FIG. 56A and FIG. 56B, andthen attached, mounted, connected, or otherwise integrated into fluidcontainer 23050 such that at least a portion of the pierceable seal23056 is contained within the fluid container 23050. The fluid container23050 may then be filled with a fluid and plugged with a plunger seal23060 at an end opposite the pierceable seal 23056. The barrel 23058 maybe filled with a fluid through the open proximal end prior to insertionof the plunger seal 23060 from the proximal end of the barrel 23058. Thedrive mechanism 23090 may then be attached to the proximal end of thefluid container 23050 such that a component of the drive mechanism 23090is capable of contacting the plunger seal 23060. The insertion mechanism23070 may be assembled and attached to the other end of the fluidconduit 23035. This entire sub-assembly, including drive mechanism23090, fluid container 23050, fluid pathway connector 23030, fluidconduit 23035, and insertion mechanism 23070, may be sterilized by knowntechniques before assembly into the drug delivery device. Certaincomponents of this sub-assembly may be mounted to an assembly platformwithin the housing 12A, 12B or directly to the interior of the housing12A, 12B, while other components may be mounted to a guide, channel, orother component or aspect for activation by the user.

Manufacturing of a fluid pump includes the step of attaching both thefluid pathway connector and fluid container, either separately or as acombined component, to an assembly platform or housing of the drug pump.The method of manufacturing further includes attachment of the drivemechanism, fluid container, and insertion mechanism to the assemblyplatform or housing. The additional components of the fluid pump, asdescribed above, including the power and control system, the activationmechanism, and the control arm may be attached, preformed, orpre-assembled to the assembly platform or housing. An adhesive patch andpatch liner may be attached to the housing surface of the drug pump thatcontacts the user during operation of the device.

A method of operating the fluid pump includes one or more of thefollowing steps: activating, by a user, the activation mechanism;displacing a control arm to actuate an insertion mechanism; activating adrive control mechanism to push the plunger seal, connect the sterilefluid pathway connector, and drive fluid flow through the fluid pump,wherein translating the fluid pathway connector causes a pierceable sealto be pierced by a piercing member thereby opening a fluid path from thefluid container to the fluid pathway connector. The drive controlmechanism may be activated by actuating a power and control system. Themethod may further include the step of: engaging an optional on-bodysensor prior to activating the activation mechanism. Furthermore, themethod of operation may include translating a plunger seal within thedrive control mechanism and fluid container to force fluid drug flowthrough the fluid container, the fluid pathway connector, a sterilefluid conduit, and, optionally the insertion mechanism for delivery ofthe fluid to the body of a user.

VIII. Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B and 33A-33C, may be configured to incorporate the embodiments ofthe drive mechanism described below in connection with FIGS. 69A-77C.The embodiments of the drive mechanism described below in connectionwith FIGS. 69A-77C may be used to replace, in its entirety or partially,the above-described drive mechanisms 100, 6100, or 8100, or any otherdrive mechanism described herein, where appropriate.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances, controlled drug delivery pumpswith such drive mechanisms, the methods of operating such devices, andthe methods of assembling such devices. Notably, the multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The embodiments of the present disclosure thus arecapable of delivering drug substances at variable rates. The drivemechanisms of the present disclosure may be pre-configurable ordynamically configurable, such as by control by the power and controlsystem, to meet desired delivery rates or profiles, as explained indetail below. Additionally, the drive mechanisms of the presentdisclosure provide integrated status indication features which providefeedback to the user before, during, and after drug delivery. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. Because theend-of-dose indication is related to the physical end of axialtranslation and/or travel of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a multi-functiondrive mechanism which includes an actuator, a gear assembly including amain gear, a drive housing, and a drug container having a cap, apierceable seal (not visible), a barrel, and a plunger seal. The maingear may be, for example, a star gear disposed to contact multiplesecondary gears or gear surfaces. A drug chamber, located within thebarrel between the pierceable seal and the plunger seal, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. A piston, and one or morebiasing members, wherein the one or more biasing members are initiallyretained in an energized state and is configured to bear upon aninterface surface of the piston, may also be incorporated in themulti-function drive mechanism. The piston is configured to translatesubstantially axially within a drug container having a plunger seal anda barrel. A tether is connected at one end to the piston and at anotherend to a winch drum/gear of a regulating mechanism, wherein the tetherrestrains the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The drug container may contain a drugfluid within a drug chamber for delivery to a user. Optionally, a coversleeve may be utilized between the biasing member and the interfacesurface of the piston to hide the interior components of the barrel(namely, the piston and the biasing member) from view during operationof the drive mechanism. The tether is configured to be released from awinch drum/gear of a regulating mechanism of the multi-function drivemechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In at least one embodiment of the present disclosure, the regulatingmechanism is gear assembly driven by an actuator of the multi-functiondrive mechanism. The regulating mechanism retards or restrains thedistribution of tether, only allowing it to advance at a regulated ordesired rate. This restricts movement of piston within barrel, which ispushed by one or more biasing members, hence controlling the movement ofplunger seal and delivery of the drug contained in chamber. As theplunger seal advances in the drug container, the drug substance isdispensed through the sterile pathway connection, conduit, insertionmechanism, and into the body of the user for drug delivery. The actuatormay be a number of power/motion sources including, for example, a motor(e.g., a DC motor, AC motor, or stepper motor) or a solenoid (e.g.,linear solenoid, rotary solenoid). In a particular embodiment, theactuator is a rotational stepper motor with a notch that correspondswith the gear teeth of the main/star gear.

The regulating mechanism may further include one or more gears of a gearassembly. One or more of the gears may be, for example, compound gearshaving a small diameter gear attached at a shared center point to alarge diameter gear. The gear assembly may include a winch gear coupledto a winch drum/gear upon which the tether may be releasably wound.Accordingly, rotation of the gear assembly initiated by the actuator maybe coupled to winch drum/gear (i.e., through the gear assembly), therebycontrolling the distribution of tether, the rate of expansion of thebiasing members and the axial translation of the piston, and the rate ofmovement of plunger seal within barrel to force a fluid from drugchamber. The rotational movement of the winch drum/gear, and thus theaxial translation of the piston and plunger seal, are metered,restrained, or otherwise prevented from free axial translation by othercomponents of the regulating element, as described herein. Notably, theregulating mechanisms of the present disclosure do not drive thedelivery of fluid substances from the drug chamber. The delivery offluid substances from the drug chamber is caused by the expansion of thebiasing member from its initial energized state acting upon the pistonand plunger seal. The regulating mechanisms instead function to provideresistance to the free motion of the piston and plunger seal as they arepushed by the expansion of the biasing member from its initial energizedstate. The regulating mechanism does not drive the delivery but onlycontrols the delivery motion. The tether limits or otherwise restrainsthe motion of the piston and plunger seal, but does not apply the forcefor the delivery.

In addition to controlling the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer (thereby delivering drug substances at variable rates and/ordelivery profiles); the multi-function drive mechanisms of the presentdisclosure may concurrently or sequentially perform the steps of:triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a user; and connecting a sterile fluid pathway to adrug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. In at least oneembodiment, initial motion by the actuator of the multi-function drivemechanism causes rotation of main/star gear. In one manner, main/stargear conveys motion to the regulating mechanism through gear assembly.In another manner, main/star gear conveys motion to the needle insertionmechanism through gear. As gear is rotated by main/star gear, gearengages the needle insertion mechanism to initiate the fluid pathwayconnector into the user, as described in detail above. In one particularembodiment, needle insertion mechanism is a rotational needle insertionmechanism. Accordingly, gear is configured to engage a correspondinggear surface of the needle insertion mechanism. Rotation of gear causesrotation of needle insertion mechanism through the gear interactionbetween gear of the drive mechanism and corresponding gear surface ofthe needle insertion mechanism. Once suitable rotation of the needleinsertion mechanism occurs, the needle insertion mechanism may beinitiated to create the fluid pathway connector into the user, asdescribed in detail herein.

In at least one embodiment, rotation of the needle insertion mechanismin this manner may also cause a connection of a sterile fluid pathway toa drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. Ramp aspect ofneedle insertion mechanism is caused to bear upon a movable connectionhub of the sterile fluid pathway connector. As the needle insertionmechanism is rotated by the multi-function drive mechanism, ramp aspectof needle insertion mechanism bears upon and translates movableconnection hub of the sterile fluid pathway connector to facilitate afluid connection therein. In at least one embodiment, the needleinsertion mechanism may be configured such that a particular degree ofrotation enables the needle/trocar to retract as detailed above.Additionally or alternatively, such needle/trocar retraction may beconfigured to occur upon a user-activity or upon movement or function ofanother component of the drug delivery device. In at least oneembodiment, needle/trocar retraction may be configured to occur uponend-of-drug-delivery, as triggered by, for example, the regulatingmechanism and/or one or more of the status readers as described herein.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug delivery pump having ahousing and an assembly platform, upon which an activation mechanism, aninsertion mechanism, a fluid pathway connector, a power and controlsystem, and a controlled delivery drive mechanism may be mounted, saiddrive mechanism having a drive housing, a piston, and a biasing member,wherein the biasing member is initially retained in an energized stateand is configured to bear upon an interface surface of the piston. Thepiston is configured to translate substantially axially within a drugcontainer having a plunger seal and a barrel. A tether is connected atone end to the piston and at another end to a winch drum/gear of adelivery regulating mechanism, wherein the tether restrains the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The drug container may contain a drug fluid within a drug chamberfor delivery to a user. Optionally, a cover sleeve may be utilizedbetween the biasing member and the interface surface of the piston tohide the interior components of the barrel (namely, the piston and thebiasing member) from view during operation of the drive mechanism. Thetether is configured to be released from a winch drum/gear of thedelivery regulating mechanism to meter the free expansion of the biasingmember from its initial energized state and the free axial translationof the piston upon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum/gear upon which the tether may be releasably wound, rotationof the winch drum/gear releases the tether from the winch drum/gear tometer the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The metering of the tether controls therate or profile of drug delivery to a user. The piston may be one ormore parts and connects to a distal end of the tether. The winchdrum/gear is coupled to a regulating mechanism which controls rotationof the winch drum/gear and hence metering of the translation of thepiston.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch drum/gear and thereby permit axialtranslation of the piston by the biasing member to translate a plungerseal within a barrel. The one or more inputs may be provided by theactuation of the activation mechanism, a control interface, and/or aremote control mechanism. The power and control system may be configuredto receive one or more inputs to adjust the restraint provided by thetether and winch drum/gear on the free axial translation of the pistonupon which the biasing member bears upon to meet a desired drug deliveryrate or profile, to change the dose volume for delivery to the user,and/or to otherwise start, stop, or pause operation of the drivemechanism.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of the actuator. The change in the rate of movement ofthe actuator causes a change in the rotation rate of the regulatingmechanism which, in turn, controls the rate of drug delivery to theuser. Alternatively, the delivery profile may be altered by a change inthe characteristics of the flow path of medicament through the conduitconnecting the drug container and insertion mechanism. The change may becaused by the introduction, removal, or modification of a flowrestrictor which restricts flow of medicament from the drug container tothe insertion mechanism. For example, a flow restrictor may havemultiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

The embodiments of the present disclosure provide drive mechanisms whichare capable of metering, providing resistance, or otherwise preventingfree axial translation of the plunger seal utilized to force a drugsubstance out of a drug container and, thereby, controlling the rate ofdelivery of drug substances. The control delivery drive mechanisms areadditionally capable of providing the incremental status of the drugdelivery before, during, and after operation of the device. Throughoutthis specification, unless otherwise indicated, “comprise,” “comprises,”and “comprising,” or related terms such as “includes” or “consists of,”are used inclusively rather than exclusively, so that a stated integeror group of integers may include one or more other non-stated integersor groups of integers. As will be described further below, theembodiments of the present disclosure may include one or more additionalcomponents which may be considered standard components in the industryof medical devices. For example, the embodiments may include one or morebatteries utilized to power the motor, drive mechanisms, and drugdelivery devices of the present disclosure. The components, and theembodiments containing such components, are within the contemplation ofthe present disclosure and are to be understood as falling within thebreadth and scope of the present disclosure.

The present disclosure provides systems and methods that are related todelivery of drug substances at a predetermined time and at an adjusteddelivery rate. Particularly, the present disclosure relates to drugdelivery device delivery devices that include control systems andsub-systems that are configured to control and drive multi-functiondrive mechanisms. Additionally, the control systems and sub-systems maybe configured to deliver drug substances at appropriate delivery ratesafter a certain wait time period has elapsed.

In one example, a user may be provided with a pre-filled drug deliverypump device to inject the drug substance via the parenteral method. Insuch an example, activation of the pump device may establish short rangecommunication with a mobile device (e.g., a smart phone). In oneembodiment, the drug delivery device delivery device may be activated bypress of an activation button or a power button. The mobile device mayinclude one or more mobile applications that may be configured toprocess, receive and transmit data related to the drug delivery process.The mobile application may communicate with external sensors (e.g., aheart rate sensor and a glucose rate sensor) and receive information(e.g., heart rate of the user, glucose/insulin information, etc.)related to the health and/or state of the patient during a monitoringperiod. The mobile application may further calculate an adjusteddelivery rate for the drug based on the data received from the sensors.

Moreover, the drug delivery device may request user-activation for theneedle insertion, after the device has been activated. The drug deliverydevice may provide visual or audio cues for the needle activation or,alternatively, cause the mobile device to provide the requestnotification for needle activation. When the needle insertion has beenactuated by the user, the drug delivery device may then initiate a timerto track a wait time period, prior to the delivery of the drug.Alternatively, the timer may be initiated upon activation of the device.The drug delivery device may optionally monitor the temperature todetermine whether the drug has reached an optimal temperature fordelivery. Additionally, the power and control system may be configuredto determine whether the predetermined wait time period has elapsed, andbased on the determination may notify the user about the initiation ofthe drug delivery process. Optionally, the user may have the option ofinitiating drug delivery after the predetermined wait time has elapsed.

It is noted that, based on the type of the drug and the dose, the drugdelivery device may regulate the delivery rate of the drug. Theregulation and/or adjustment of the delivery rate may also be based oninformation received from sensors (e.g., temperature sensor, heart ratesensor, glucose monitor sensor).

The drug delivery device may further determine whether the drug deliveryhas ended, and based on the determination, may transmit the end of drugdelivery information to the mobile device.

The mobile device may further provide the received end of deliveryinformation to a remote server (e.g., a cloud computer server). The endof delivery information may include, but not limited to, end of deliveryindication, delivery rate, delivery start and end times, total deliverytime, drug temperature, and data gathered by the sensors. Theinformation may also include information related to the drug and/or pumpdevice such as drug volume, manufacturing date, filling date, serial/lotnumber, etc.

Moreover, the drug delivery device may switch between an active powermode and a non-active power mode. During the active power mode, thepower and control system may interact with one or more motors of a drivecontrol system to actuate one or more drive mechanisms, and as such,both the power and control system and the motors may receive power froman energy source (e.g., batteries). On the other hand, in someinstances, the power and control system may not need to interact withthe drive control system to execute one or more operations of the drugdelivery pump device. For example, the drug delivery device mayestablish and communicate with the mobile device, or monitor temperatureof the drug without interacting with the drive control system of thedrug delivery device. In such instances, the power and control systemmay only be powered, and the drive control system may not receive powerfrom the batteries. Additionally, one or more components or functions ofthe pump device may be powered intermittently in one or more modes.

The switching between the active power mode and the non-active powermode may substantially save power resources of the drug delivery device.For example, upon switching to the non-active power mode, the drugdelivery device does not need to provide power to the motors, which may,otherwise, significantly drain the batteries.

Particularly, during the active power mode, the power and control systemof the drug delivery pump device controls the multi-function drivemechanisms to initiate several sub-systems or functions, including: (i)controlling the rate of drug delivery by metering, providing resistance,or otherwise preventing free axial translation of the plunger sealutilized to force a drug substance out of a drug container; (ii)triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a user; and (iii) connecting a sterile fluid pathway toa drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user.

The drive mechanisms of the present disclosure control the rate of drugdelivery by metering, providing resistance, or otherwise preventing freeaxial translation of the plunger seal utilized to force a drug substanceout of a drug container and, thus, are capable of delivering drugsubstances at variable rates and/or delivery profiles. Additionally, thedrive mechanisms of the present disclosure may include integrated statusindication features, such as sensors, which may provide feedback to thepower and control system, and in turn, to the user before, during, andafter drug delivery. For example, the user may be prompted by one ormore sensors to identify that the devices are operational and ready fordrug delivery. Upon activation of one or more devices, the sensors mayprovide one or more drug delivery status indications to the user such asan end-of-dose indication at completion of drug delivery.

As used herein to describe the drive mechanisms, drug delivery pumps, orany of the relative positions of the components of the presentdisclosure, the terms “axial” or “axially” refer generally to alongitudinal axis “A” around which the drive mechanisms are preferablypositioned, although not necessarily symmetrically there-around. Theterm “radial” refers generally to a direction normal to axis A. Theterms “proximal,” “rear,” “rearward,” “back,” or “backward” refergenerally to an axial direction in the direction “P”. The terms“distal,” “front,” “frontward,” “depressed,” or “forward” refergenerally to an axial direction in the direction “D”. As used herein,the term “glass” should be understood to include other similarlynon-reactive materials suitable for use in a pharmaceutical gradeapplication that would normally require glass, including but not limitedto certain non-reactive polymers such as cyclic olefin copolymers (COC)and cyclic olefin polymers (COP). The term “plastic” may include boththermoplastic and thermosetting polymers. Thermoplastic polymers can bere-softened to their original condition by heat; thermosetting polymerscannot. As used herein, the term “plastic” refers primarily to moldablethermoplastic polymers such as, for example, polyethylene andpolypropylene, or an acrylic resin, that also typically contain otheringredients such as curatives, fillers, reinforcing agents, colorants,and/or plasticizers, etc., and that can be formed or molded under heatand pressure. As used herein, the term “plastic” is not meant to includeglass, non-reactive polymers, or elastomers that are approved for use inapplications where they are in direct contact with therapeutic liquidsthat can interact with plastic or that can be degraded by substituentsthat could otherwise enter the liquid from plastic. The term“elastomer,” “elastomeric” or “elastomeric material” refers primarily tocross-linked thermosetting rubbery polymers that are more easilydeformable than plastics but that are approved for use withpharmaceutical grade fluids and are not readily susceptible to leachingor gas migration under ambient temperature and pressure. “Fluid” refersprimarily to liquids, but can also include suspensions of solidsdispersed in liquids, and gasses dissolved in or otherwise presenttogether within liquids inside the fluid-containing portions of the drugpumps. According to various aspects and embodiments described herein,reference is made to a “biasing member”, such as in the context of oneor more biasing members for asserting force on a plunger seal. It willbe appreciated that the biasing member may be any member that is capableof storing and releasing energy. Non-limiting examples include a spring,such as for example a coiled spring, a compression or extension spring,a torsional spring, or a leaf spring, a resiliently compressible orelastic band, or any other member with similar functions. In at leastone embodiment of the present disclosure, the biasing member is aspring, preferably a compression spring.

The devices of the present disclosure provide drive mechanisms withintegrated status indication and drug delivery pumps which incorporatesuch drive mechanisms. Such devices are safe and easy to use, and areaesthetically and ergonomically appealing for self-administeringpatients. The devices described herein incorporate features which makeactivation, operation, and lock-out of the device simple for evenuntrained users. The devices of the present disclosure provide thesedesirable features without any of the problems associated with knownprior art devices. Certain non-limiting embodiments of the drug deliverypumps, drive mechanisms, and their respective components are describedfurther herein with reference to the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.69A-69C show an exemplary drug delivery device according to at least oneembodiment of the present disclosure with the top housing removed sothat the internal components are visible. The drug delivery device maybe utilized to administer delivery of a drug treatment into a body of auser. As shown in FIGS. 69A-69C, the drug delivery device 9010 includesa pump housing 9012. Pump housing 9012 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug pump. For example,drug delivery device 9010 includes a pump housing 9012 which may includean upper housing and a lower housing (not shown for ease of viewinginternal components). The pump housing 9012 may include one or moretamper evidence features to identify if the drug delivery device hasbeen opened or tampered with. For example, the pump housing 9012 mayinclude one or more tamper evidence labels or stickers, such as labelsthat bridge across the upper housing and the lower housing. Additionallyor alternatively, the housing 9012 may include one or more snap arms orprongs connecting between the upper housing and the lower housing. Abroken or altered tamper evidence feature would signal to the user, thephysician, the supplier, the manufacturer, or the like, that the drugdelivery device has potentially been tampered, e.g., by accessing theinternal aspects of the device, so that the device is evaluated andpossibly discarded without use by or risk to the user. The drug deliverydevice may further include an activation mechanism, a status indicator,and a window. Window may be any translucent or transmissive surfacethrough which the operation of the drug delivery device may be viewed.As shown in FIG. 69B, drug delivery device 9010 further includesassembly platform 9020, sterile fluid conduit 9030, drive mechanism90100 having drug container 9050, insertion mechanism 90200, fluidpathway connector 90300, and a power and control system (not shown). Oneor more of the components of such drug delivery devices may be modularin that they may be, for example, pre-assembled as separate componentsand configured into position onto the assembly platform 9020 of the drugdelivery device 9010 during manufacturing.

The pump housing 9012 contains all of the device components and providesa means of removably attaching the device 9010 to the skin of the user.The pump housing 9012 also provides protection to the interiorcomponents of the device 9010 against environmental influences. The pumphousing 9012 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9012 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9012 may include certaincomponents, such as one or more status indicators (e.g., LED lights,audio tones via speakerphones) and windows, which may provide operationfeedback to the user.

In one example, the power and control system may be configured toprovide a number of different status indications to the user. Forexample, the power and control system may be configured such that afterthe on-body sensor (e.g., skin sensor) is triggered, the power andcontrol system provides a ready-to-start status signal via the statusindicator (e.g., audio tones and/or blinking lights) if device start-upchecks provide no errors. After providing the ready-to-start statussignal and, in an embodiment with the optional on-body sensor, if theon-body sensor remains in contact with the body of the user, the powerand control system will power the drive mechanism 90100 to begindelivery of the drug treatment through the fluid pathway connector 90300and sterile fluid conduit 9030.

Additionally, the power and control system may be configured to identifyremoval of the drug delivery device from its packaging. The power andcontrol system may be mechanically, electronically, orelectro-mechanically connected to the packaging such that removal of thedrug delivery device from the packaging may activate or power-on thepower and control system for use, or simply enable the power and controlsystem to be powered-on by the user. In such an embodiment, withoutremoval of the drug delivery device from the packaging the drug deliverydevice cannot be activated. This provides an additional safety mechanismof the drug delivery device and for the user. In at least oneembodiment, the drug delivery device or the power and control system maybe electronically or electro-mechanically connected to the packaging,for example, such as by one or more interacting sensors from a range of:Hall effect sensors; giant magneto resistance (GMR) or magnetic fieldsensors; optical sensors; capacitive or capacitance change sensors;ultrasonic sensors; and linear travel, LVDT, linear resistive, orradiometric linear resistive sensors; and combinations thereof, whichare capable of coordinating to transmit a signal between components toidentify the location there-between.

Additionally or alternatively, the drug delivery device or the power andcontrol system may be mechanically connected to the packaging, such asby a pin and slot relationship which activates the system when the pinis removed (i.e., once the drug delivery device is removed from thepackaging).

In a preferred embodiment of the present disclosure, once the power andcontrol system has been activated, and after a predetermined wait timeperiod, the multi-function drive mechanism is initiated to actuate thedrug fluid to be forced from the drug container.

During the drug delivery process, the power and control system may befurther configured to provide a dispensing status signal via the statusindicator. After the drug has been administered into the body of theuser and after the end of any additional dwell time, to ensure thatsubstantially the entire dose has been delivered to the user, the powerand control system may provide an okay-to-remove status signal via thestatus indicator. This may be independently verified by the user byviewing the drive mechanism and drug dose delivery through the window ofthe pump housing 9012. Additionally, the power and control system may beconfigured to provide one or more alert signals via the statusindicator, such as for example alerts indicative of fault or operationfailure situations.

The power and control system may additionally be configured to acceptvarious inputs (e.g., via an activation button) from the user todynamically control the drive mechanisms 90100 to meet a desired drugdelivery rate or profile. For example, the power and control system mayreceive inputs, such as from partial or full activation, depression,and/or release of the activation mechanism, to set, initiate, stop, orotherwise adjust the control of the drive mechanism 90100 via the powerand control system to meet the desired drug delivery rate or profile.Similarly, the power and control system may be configured to receivesuch inputs to initiate communication with the mobile device, adjust thedrug dose volume, to prime the drive mechanism, fluid pathway connector,and fluid conduit; and/or to start, stop, or pause operation of thedrive mechanism 90100. Such inputs may be received by the user directlyacting on the drug delivery device 9010, such as by use of theactivation mechanism 9014 or a different control interface, or the powerand control system may be configured to receive such inputs from aremote device (e.g., a mobile device). Additionally or alternatively,such inputs may be pre-programmed.

Other power and control system configurations may be utilized with thedrug delivery devices of the present disclosure. For example, certainactivation delays may be utilized prior to, or during drug delivery. Forexample, a wait-time period may be a pre-determined time that may be setin the power and control system, and which may delay the delivery of thedrug by the pre-determined amount of time. As mentioned above, one suchdelay optionally included within the system configuration is a dwelltime which ensures that substantially the entire drug dose has beendelivered before signaling completion to the user. Similarly, activationof the device may require a delayed depression (i.e., pushing) of theactivation mechanism of the drug delivery device 9010 prior to drugdelivery device activation. Additionally, the system may include afeature which permits the user to respond to the end-of-dose signals andto deactivate or power-down the drug delivery device. Such a feature maysimilarly require a delayed depression of the activation mechanism, toprevent accidental deactivation of the device. Such features providedesirable safety integration and ease-of-use parameters to the drugdelivery devices. An additional safety feature may be integrated intothe activation mechanism to prevent partial depression and, therefore,partial activation of the drug delivery devices. For example, theactivation mechanism and/or power and control system may be configuredsuch that the device is either completely off or completely on, toprevent partial activation. Such features are described in furtherdetail hereinafter with regard to other aspects of the drug deliverydevices.

In one embodiment, the drug delivery pump device 9010 may include one ormore control systems such as, but not limited to, power and controlsystem 90800 and drive control system 90820. As disclosed above, thedrug delivery pump 9010 may further include various mechanisms orsub-systems such as, but not limited to, drive mechanism or sub-system90100, needle insertion mechanism (NIM) or sub-system 90200, sterilefluid pathway connector (SFPC) or sub-system 90300, and regulatingmechanism or sub-system 90500. In some examples, the control systems mayinclude printed circuit board (PCB), motherboards and/or daughterboards.

In some embodiments, the sub-systems may be included in the controlsystems. For example, the drive control system 90820 may include thedrive sub-system 90100, NIM sub-system 90200, and/or the regulatingsub-system 90500. In such examples, the power and control system 90800may control the sub-systems by sending command signals to the drivecontrol system 90820.

In other examples, the drive control system 90820 may not include thesub-systems. As such, in those examples, the power and control system90800 may control the sub-systems via the drive control system 90820.For example, the power and control system 90800 may send command signalsto the drive control system 90820. The drive control system 90820, forexample, may then selectively control one or more of the sub-systemsbased on the received command signals from the power and control system90810.

Yet in another embodiment, the power and control system 90800 maydirectly control the sub-systems. In that embodiment, the sub-systemsmay include respective control units or controller and storage units(not shown) that may be configured to directly communicate with thepower and control system 90800.

Alternatively, in some implementations, the power and control system90800 may include the drive control system 90820 and the sub-systems,and one or more other control systems and sub-systems.

As shown in FIG. 76A, in one exemplary embodiment, the power and controlsystem 90800 may be included in the drug delivery pump 9010. The powerand control system 90800 may include one or more control units that areconnected to one or more sensors, timers and storage units of the drugdelivery pump 9010.

In some implementations, the power and control system 90800 may beconfigured to control a delay time period related to drug delivery. Insuch implementations, the power and control system 90800 may monitor andcontrol time parameters for initiating and delivering the drug after theactivation of the drug delivery pump 9010. For example, upon theactivation of the device 9010, the power and control system 90800 maymonitor a wait period time (e.g., a predetermined delay time) prior tothe initiation of the drug delivery. In one example, during the waitperiod, the power and control system 90800 may optionally prime thedevice.

In one example, the power and control system 90800 may provide requestnotification to activate the NIM mechanism after the device has beenactivated. The request notification may be provided directly by the drugdelivery device delivery device 9010, or via the mobile device 9011.Upon notifying the user to initiate the NIM mechanism 90200, the powerand control system may further determine whether anactivation/initiation signal (e.g., from the user) is received via theactivation button.

When the power and control system 90800 determines that the activationsignal is received (e.g., within an NIM activation predetermined time),the power and control system may cause the NIM sub-system to activate.Alternatively, the NIM may be directly activated by the user. The powerand control system 90800 may further notify the user that the deliveryof the drug has been initiated. It is noted that, the power and controlsystem 800 may activate the NIM mechanism upon receiving the activationsignal related for the NIM activation and, upon further receiving signalfrom on-body sensor that indicates that the drug delivery device 9010 issensing the skin of the user. Optionally, when the power and controlsystem determines that the activation signal is not received, and/or theon-body sensor is not sensing a skin portion of the user, the power andcontrol system 90800 may notify the user (e.g., via an audible tone),and optionally terminate drug delivery process.

Moreover, in some implementations, when the power and control system90800 determines that the wait period time has elapsed, the power andcontrol system may notify the user about the initiation of the deliveryof the drug. The power and control system may further notify the userthat the delivery of the drug has been initiated.

Optionally, the power and control system 90800 may further notify theuser of a time period of the drug delivery (e.g., the total time thatwill be taken for delivering the drug). The power and control system90800 may communicate the notification to an external device via thecommunication unit 90830.

Upon the initiation of the drug delivery, the power and control systemmay further control timing and/or rate parameters for the drug delivery.For example, the power and control system may control the regulatingsub-system or mechanism to deliver the drug in a given period of time.Moreover, the power and control system may process various data capturedby the internal and external sensors to determine the timing and/or rateparameters for the drug delivery. Based on the determination, the powerand control system may deliver the drug to the user within theappropriate time period.

The power and control system may or may not include all the elements ofthe power and control system 90800, and/or may include additionalelements. Additionally, in some examples, the drug delivery device 9010may include one or more control systems, including, but not limited to,the power and control system, and may include additional elements forthe operations of the drug delivery device.

In some implementations, control system 90800 may include a main controlunit or control unit 90810. The main control unit 90810 may include oneor more controllers, microcontrollers, microprocessors, or applicationspecific integrated circuits (ASICs). Main control unit 90810 may beimplemented as hardware or a combination of hardware and software thatmay be programmed with instructions. The main control unit 90810 may beconfigured to execute such instructions to effect various operations ofthe drug delivery device 9010. Moreover, the power and control system orthe main control unit 90810 may communicate, for example, by receivingand/or sending signal or data to and from the communication unit 90830,timer unit 90812, storage unit 90813, on-body sensor 90840, temperaturesensor 90880, and I/O unit 90850. The main control unit 90810 mayprocess and interpret the data collected or monitored by the variouselements in the one or more control systems in order to determine andexecute various functions and operations of the drug delivery device9010.

It is noted that, the drug delivery device 9010 may operate in two powermodes, namely, an active power mode and a non-active power mode. Duringthe active power mode, the power and control system 90800 and the motor90101 may receive power from the power source (e.g., batteries), and thepower and control system 90800 may command the drive control system90820 to drive various operations, such as the NIM mechanism 90200,and/or regulating mechanism 90500. Whereas, during the non-active powermode, the power and control system 90800 may be powered, and the motor90101 may not be powered. During the non-active power mode, the powerand control system 90800 may execute various operations of the drugdelivery device 9010 that may not require operations related to themotor 90101. For example, the power and control system 90800 mayestablish communication link with the mobile device 9011, and furthercommunicate intermittently or continuously with the mobile device 9011during the non-active power mode. Additionally, during the non-drivemode, the power and control system 90800 may provide notifications, andalert to the user, and may further communicate with the various sensors(e.g., the temperature sensor and on-body sensor), and/or determinetimings of various operations. Optionally, the drug delivery device 9010may be primed during the non-active power mode.

Moreover, the drug delivery device 9010 may switch between the activepower mode and the non-active power mode.

The different power modes may be initiated, based on: (a) type ofactivation (e.g., device activation, activation of the drug delivery,control of the drug delivery, initiation of the timer, etc.), (b)predetermined time set (e.g., after, or, during the wait time period),and/or (c) operations (e.g., communication with the mobile device and/orsensors, control of the various operations by the power and controlsystem 90800) of the drug delivery device 9010. Alternatively, theactivation and/or switching between the modes may be performed manuallyby the user of the drug delivery device 9010.

It will be appreciated that, by appropriately powering up the motor90101 and the power and control system 90800, the overall powerrequirement of the drug delivery device 9010 may be reduced. Forexample, powering the motor 90101 while the motor 90101 is idle mayprematurely drain the power source or battery of the drug deliverydevice 9010. As such, by managing the power cycle, for example, byproviding power to the motor 90101 only when activities related to themotor 90101 are initiated, the life of the battery to operate the drugdelivery device 9010 may be suitably increased or the demand for powerto operate the drug delivery device 9010 over the life of the drugdelivery period may be significantly reduced.

Timer unit 90812 may be a digital clock that may be programmed, forexample, to set up time periods for various operations of the drugdelivery device 9010. For example, the timer unit 90812 may beconfigured to indicate, to the main control unit 90810, a wait time or adelay period time for a drug (i.e., a time period before the drug can beforced to be delivered).

Additionally, timer unit 90812 may indicate a time-out period forreceiving an activation signal (i.e., a time period within which a usermay provide an activation signal to initiate drug delivery or NIM90200). In some embodiments, timer unit 90812 may directly communicatewith the control units of various sensors. In some implementations, thetimer unit 90812 may be included in the main control unit 90810.

Control system 90800 may include storage unit 90813. Storage unit 90813may include one more storage units, such as a random access memory (RAM)or other dynamic storage device, and/or a read only memory (ROM), and/oran electrically erasable programmable read only memory (EEPROM) forstoring temporary parameters, information and instructions for the maincontrol unit 90810. In some implementations, the storage unit may beimplemented as a non-transitory computer readable medium which storesinstructions that may be processed and executed by the control unit tocontrol operations of the control system of the drug delivery device.Additionally, storage unit 90813 may store error codes or errornotification for various operations associated with the sensors andcontrol unit of the drug delivery device 9010. The error codes may bepre-programmed into the storage unit 90813.

Storage unit 90813, may additionally, store various predetermined delayor wait time periods related to the drug delivery.

In some examples, power and control system 90800 may includecommunication unit 90830. Communication unit 90830 may include one ormore 90802.11 Wi-Fi transceivers, a cellular transceiver, IEEE 90802.14ZigBee transceiver, a Bluetooth transceiver, and/or a Bluetooth LowEnergy (BLE) transceiver, and for other wireless communicationprotocols, such as near-field communication (NFC), infrared orultrasonic. The drug delivery device 9010 may include appropriateantenna (not shown), for communication with an external computer device,and may receive/transmit data via the communication unit 90830.

As shown in FIG. 76D, the drug delivery device 9010 may communicate withan external computing device (via the communication unit 90830). Theexternal computing device may be mobile computing device 9011 such as asmart phone which may include various mobile applications and may beconfigured with the appropriate communication protocols.

In one example, the mobile device 9011 may include a pump device mobileapplication (app) 9010 a that communicates with the drug delivery device9010. In such an example, the mobile app 9010 a may be provided (fromthe manufacturer of the drug or drug delivery device 9010) to the userupon purchasing the drug or the drug delivery device 9010. For example,the container or the box of the drug delivery device 9010 may include aunique download identifier that the user may use to download the drugdelivery device mobile app 10 a. For example, the user may use thedownload identifier to download the app 9010 a from Apple Store orGoogle Play store.

Upon downloading the drug delivery device app 9010 a to the mobiledevice 9010 a, the user may communicate with the drug delivery device9010 using the drug delivery device application 9010 a (e.g., uponestablishing a wireless communication link with the drug delivery device9010). The mobile app 9010 a may be configured to cause the mobiledevice 9011 to process various information received from the drugdelivery device 9010, external entities, such as sensors 9011 a and 9011b, and/or optionally data received from a cloud server. Based on theprocessing of such data, the mobile app 9010 a may cause the mobiledevice 9011 to transfer appropriate data to the external cloud server9011 c. Mobile app 10 a may further cause the mobile device 9011 todisplay appropriate notification to the user based on the processing ofsuch data.

In one example, the user may optionally select the activation button9010 b to establish a short range wireless connection with the drugdelivery device 9010. In one example, the activation button 9010 b mayinitiate a Bluetooth discovery and pairing process for the mobile device9011.

Moreover, when the drug delivery device 9010 is activated and incommunication with the mobile device 9011, mobile app 9010 a may receivea notification from the drug delivery device 9010 (via the communicationunit 90830) that indicates activation of the drug delivery device 9010.In some examples, activation button 9010 b may additionally beconfigured to initiate, modify and/or terminate various mechanisms ofthe drug delivery process.

In some examples, drug delivery device app 9010 a may gather and providevarious time period information of the drug delivery process to theuser. Particularly, in one example, selection of the timer button 9010 cmay provide information related to various timing periods related to thedrug delivery process. The timer button 9010 c may be triggered, in oneexample, upon the selection of the activation button 10 b. In oneexample, the selection of the timer button 9010 c may evoke a clock orstop watch application of the mobile device 9011.

In one example, upon the activation of the drug delivery device 9010 andthe initiation of the timer unit 90812, the user may gather informationrelated to the predetermined wait time period prior to the initiation ofthe drug delivery.

Optionally, drug delivery device app 9010 a may provide alarmnotification. For example, the timer button 9010 c may be configured toprovide alarm notification prior to the initiation of the drug deliveryprocess. In one example, the user may optionally indicate how often toreceive alarm notification prior to the drug delivery process. Timerbutton 9010 c may be further configured to indicate the delivery timeperiod when the drug is being delivered to the user.

Moreover, drug delivery device app 9010 a may be configured to receiveinformation, for example, from the drug delivery device 9010. Forexample, a user may select the Tx/Rx notification and data button 9010 dto receive notification related to the drug delivery process (e.g., fromthe drug delivery pump device 9010), and transmit information related tothe drug delivery process (e.g., to the cloud server 9011 c).

In one example, upon the selection of the Tx/Rx button 9010 d, the usermay view notification related to the drug delivery process, such as theactivation of the drug delivery device 9010, and/or end of dosenotification.

Additionally, the user may view data via the Tx/Rx button 9010 d relatedto the drug delivery process, such as the rate at which the drug wasdelivered, the total time period of the delivery process. In oneexample, the user may further transfer the data and/or notification to acloud server 9011 c of relevant entities (e.g., physician, healthinsurance company, etc.) In such a scenario, the drug delivery deviceapplication 9010 a may evoke the communication interface (e.g., acellular communication interface) of the mobile device 9011 tocommunicate such information that is received from drug delivery device9010 to the external cloud server 9011 c.

In one example, the mobile app 9010 a may collect information from othersensors that are local or external to the mobile device. For example,the mobile app 9010 a may collect information from a wireless heart ratesensor 9011 a, a wireless glucose rate monitor 9011 b and cause themobile device 9011 to process such information. Based on the processedinformation, the mobile app 9010 a may determine delivery rate for thedrug, and provide instruction to the user about the delivery rateinformation and activation inputs for the drug delivery device 9010.

It is contemplated that, the drug delivery device 9010 may wirelesslycommunicate with the heart rate sensor 9011 a and/or the glucose ratemonitor 9011 b and process the received information to determine thedrug delivery rate for the drug.

Referring back to FIG. 76A the power and control system 90800 mayinclude on-body sensors 90840, such as mechanical, electro-mechanicalskin sensors, and/or electrical skin sensors, for example, capacitiveskin sensor. In one example, the on-body sensor 90840 may be configuredto detect whether the pump device 9010 is in contact with the skin ofthe patient. Based on the determination, the on-body sensor may provideappropriate indication (e.g., signals) to the control unit 90810. Thecontrol unit 90810 may then control various functions of the drugdelivery device 9010. For example, the control unit 90810 may notify theuser to initiate a delivery of the drug only when the pump device 9010is in contact with the skin of the user. This may be a safety feature ofthe drug delivery device 9010, as the drive control system 90820 may notbe activated until the power and control system receives a signal fromthe on-body sensor 90840.

In one example, on-body sensor 90840 may be a mechanical switch, and thedepression of the mechanical on-body sensor 90840 may trigger theactivation of the power and control system 90810, and/or the drivecontrol system 90820. In another embodiment, the on-body sensor may be acapacitive- or impedance-based skin sensor, and the power and controlsystem and/or the drive control system 90820 may be functional uponreceiving signal from the on-body sensor. These concepts are notmutually exclusive and one or more combinations may be utilized withinthe breadth of the present disclosure to prevent, for example, prematureactivation of the drug delivery device 9010. In a preferred embodiment,the drug delivery device 9010 utilizes one or more mechanical on-bodysensors. Additional integrated safety mechanisms are described hereinwith reference to other components of the drug delivery devices.

Power and control system 90800 may optionally include one or moretemperature sensors 90880. The temperature sensor 90880 may be suitablypositioned near the drug or the drug container 9050, and configured todetect the temperature of the drug. The temperature sensor may bethermocouples or thermistors (i.e., resistors whose resistances varysignificantly with temperature), and electrically coupled to the controlunit 90810. The control unit 90810 may process the detected temperatureinformation that is received from the temperature sensor 90880 tocontrol various operations of the drug delivery device 9010. In oneexample, based on the detected temperature of the drug, the control unit90810 may notify the user to initiate the delivery of the drug prior to,or after a predetermined time has elapsed. In such a scenario, thecontrol unit 90810 may be configured to override the pre-defined waitperiod time related to the drug delivery.

The power and control system 90800 may include a power source, such asbatteries (not shown), that provides power to various electricalcomponents of the drug delivery device 9010.

Moreover, the input/output electro-mechanical unit 90850 may include anactivation button, one or more feedback mechanisms, for example, audiblealarms such as piezo alarms and/or light indicators such as lightemitting diodes (LEDs).

In one embodiment, the control unit 90810 of the power and controlsystem 90800 interfaces with the mechanical on-body sensor 9024 or theelectrical and/or electro mechanical on-body sensor 90840 to identifywhen the device is in contact with the user and/or the activationmechanism to identify when the device has been activated.

The power and control system 90800 interfaces and controls the drivecontrol system 90820 through one or more interconnects to relay statusindication, such as activation, drug delivery, and end-of-dose, andreceives status feedback from the drive control system. The statusindication or the status feedback may be presented to the user via theI/O unit 90850, such auditory tones or alarms, and/or via visualindicators, such as through the LEDs.

In one embodiment, the control interfaces between the power and controlsystem 90800 and the other components of the drive control system 90820are not engaged or connected until activation by the user (e.g., via theactivation button). This is a desirable safety feature that preventsaccidental operation of the drug delivery device, and may additionallymaintain and save the battery power during storage, transportation, andthe like.

In one implementation, upon activation of the drug delivery device 9010(e.g., via the activation button of the I/O unit 90850), themulti-function drive mechanism 90100 of the drive control system 90820is activated to: insert a fluid pathway into the user; enable, connect,or open necessary connections between a drug container, a fluid pathway,and a sterile fluid conduit; and force drug fluid stored in the drugcontainer through the fluid pathway and fluid conduit for delivery intoa user. In at least one embodiment, such delivery of drug fluid into auser is performed by the drive control system multi-function drivemechanism in a controlled manner (e.g., via the flow rate controlsub-system 90825).

FIG. 76B illustrates an exemplary drive control system 90820 that may beconfigured to drive and control various mechanical andelectro-mechanical components of the drug delivery device 9010. One ormore components of the power and control system 90800 (e.g., the controlunit 90810) may interface with the drive control system 90820, andinstruct the actuator/motor 90101 to drive various elements of the drugdelivery device 9010.

In some embodiments, control unit 90810 is electrically coupled andconfigured to communicate with motor 90101, and any other elements ofthe drive control system 90820.

In some examples, the drive control system 90820 may optionally includevarious sensors such as, but not limited to, pressure sensor 90870 (notshown) that may be configured to provide information of the pressure inthe container 9050, tether sensor 90875 (not shown) that may beconfigured to provide a status information of the tether 90525 and avalve sensor 90877 (not shown) that may be configured to provide astatus information of the valve (not shown) that may be provided on thecontainer. The sensors 90870, 90875 and 90877 may be electrical and/orelectro-mechanical components and may communicate with the control unit90810 by providing status signals corresponding to the respectivesensors. The control unit 90810 may process such signals to executeand/or delay execution of the control of various sub-systems via themotor 90101.

In one example, the drive control system 90820 may optionally includetimer unit 90860. Timer unit 90860 may be a digital clock that iscoupled to the control unit 90810. In one example, the timer unit 90860may be included in the control unit 90810. In some examples, the timerunit 90860 may be the same as timer unit 90812.

The drive control system may include an actuator or motor 90101. Theactuator 90101 may be a number of power/motion sources including, forexample, a solenoid, a stepper motor, or a rotational drive motor. Inone embodiment, the actuator 90101 is a rotational stepper motor with anotch that corresponds with the gear teeth of the main/star gear 90102.Commonly, such a rotational stepper motor may be referred to as a‘Pac-Man’ motor.

In some embodiments (see FIGS. 69A-73D), the actuator 90101 is invertical alignment and in direct engagement with the main/star gear90102. As would be readily appreciated by one having ordinary skill inthe mechanical arts, the actuator 90101 could be modified to be inhorizontal alignment. Additionally or alternatively, the actuator 90101may be modified to be in indirect engagement with the main/star gear90102, as discussed below with reference to FIG. 75.

With reference to FIG. 76C, the drive control system 90820 may controlthe multiple drive mechanisms of the drug delivery device 9010. In oneexample, the drive control system may control the drive mechanism orsub-system 90100 to control the NIM or sub-system 90200, establish theSFPC 90300 and further control the regulating mechanism 90200 of thedrug delivery device 9010.

In one example, the initiation time of the needle insertion mechanism90200, time to establish the fluid pathway connector 90300, and a drugdelivery rate of the drug may be determined by the power and controlsystem 90800 based on the various inputs received by the power andcontrol system from external sensors (e.g., the glucose rate, heartrate, etc.) The power and control system 90800 may then transmit theappropriate command signals and information (e.g., the delivery rateinformation) to the drive control system 90820.

Furthermore, the storage unit 90865 of the drive control system 90820,and/or the storage unit 90813 may store, in a lookup table and/ordatabase, pre-programmed configurations and setting information such asratio of gear assembly information (e.g., ratio of gear assembly 90516),rate of rotation of gear information (e.g., rate of rotation of the mainstar gear 90102), and diameter information of gears and drums. As such,upon receiving the delivery rate information, the control unit 90810 mayconsult the storage unit 90865 or storage unit 90813 to identify andselect the appropriate configuration of the gear assembly and the motorfrom the lookup table or the database. Based on the selection, thecontrol unit 90810 may drive the motor 90101 to control the drivemechanism 90100, NIM mechanism 90200 and the regulating mechanism 90500to deliver the drug at the desired rate.

Moreover, the drive control system 90820 may interact with the power andcontrol system 90810 and receive command signals after a predeterminedtime to control the various drive mechanisms of the drug delivery device9010.

For example, the drive control system 90820 may receive the commandsignal and timing information to control or initiate the drivingmechanism after a predetermined time. In this example, the control unit90810 may consult the timer unit 90860 or timer unit 90812 to determinethe initiation time of the activation of the drive mechanism. Upondetermination, control unit 90810 may command the actuator/motor 90101after the predetermined time to initiate a drug delivery process bycontrolling the drive mechanisms as discussed below.

After the initiation of the drug delivery, the control unit 90810 mayfurther consult the timer unit 90860 or timer unit 90812 to complete thedrug delivery in a predetermined time. The power and control system90800 may determine the timing periods, and may send command signals tothe drive control system 90820 prior to, during, and after the drugdelivery process to control the drug delivery process.

It is noted that, the drive mechanism 90100, insertion mechanism 90200,fluid pathway connector 90300 and the regulating mechanism 90500 may becontrolled by the drive control system 90820, concurrently, sequentiallyand/or non-sequentially, based on a timing period set by the power andcontrol system 90810.

In some examples, the drive control system 90820 may drive or controlthe insertion mechanism or sub-system 90200 via the drive mechanism90100. The controlling of the insertion mechanism 90200 may be performedbased on the predetermined wait time period or delay time period, eitherdirectly by the power and control system 90810, or by the drive controlsystem 90820.

In one example, the drive control system 90820 may additionally controlthe insertion mechanism 90200 to concurrently provide a fluid pathwayconnector for drug delivery to a user.

Alternatively, the drive control system 90820 may separately (and priorto or after the insertion mechanism 90200) establish the sterile fluidpathway connector 90300 by connecting a sterile fluid pathway to a drugcontainer to permit fluid flow from the drug container to the needleinsertion mechanism for delivery to the user. Details of the control ofthe insertion mechanism 90200 are discussed below.

VIII.A. Insertion Mechanism:

A number of insertion mechanisms may be utilized within the drugdelivery devices to activate the needle insertion into the body of thepatient. The pump-type delivery devices of the present disclosure may beconnected in fluid flow communication to a patient or user, for example,through any suitable hollow tubing. A solid bore needle may be used topierce the skin of the patient and place a hollow cannula at theappropriate delivery position, with the solid bore needle being removedor retracted prior to drug delivery to the patient. The fluid may beintroduced into the body through any number of means, including but notlimited to: an automatically inserted needle, cannula, micro-needlearray, or infusion set tubing.

In one example, the control unit 90810 of the power and control system90800 may receive activation inputs to initiate the drug delivery device9010. After a predetermined time or after the determination that theon-body sensor 90840 is sensing a skin portion of the user, the powerand control system 90800 may instruct the drive control system 90820 toinitiate the NIM 90200. After the wait time period, the control unit90810 may actuate one or more biasing members to initiate the needleinsertion mechanism or sub-system 90200. For example, a biasing membersuch as a spring may be actuated by the motor 90101 to providesufficient force to cause the needle and cannula to pierce the skin ofthe patient. The same spring, an additional spring, or another similarmechanism may be utilized to retract the needle from the patient.

In one embodiment, the power and control system 90800 and/or the drivecontrol system 90820 may actuate the insertion mechanism 90200 asdescribed in International Patent Application No. PCT/US2012/53174,which is included by reference herein in its entirety for all purposes.Such a configuration may be utilized for insertion of the drug deliverypathway into, or below, the skin (or muscle) of the patient in a mannerthat minimizes pain to the patient. Other known methods for insertion ofa fluid pathway may be utilized and are contemplated within the boundsof the present disclosure, including a rigid needle insertion mechanismand/or a rotational needle insertion mechanism as developed by theassignee of the present disclosure.

In at least one embodiment, the insertion mechanism 90200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 69B and FIG. 69C). The connection of the base to theassembly platform 9020 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9010. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9030 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9027 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane (not visible).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. In one example, the power andcontrol system 90800 may send command signals to the drive controlsystem 90820 to initiate the needle insertion mechanism 90200 after thewait time period. Upon receiving the command signal, the actuator 90101may cause displacement of the lockout pin(s), such as pulling, pushing,sliding, and/or rotation. This may cause the insertion biasing member todecompress from its initial compressed, energized state. Particularly,the decompression of the insertion biasing member drives the needle and,optionally, the cannula into the body of the user. At the end of theinsertion stage or at the end of drug delivery (as triggered by themulti-function drive mechanism 90100 and/or the regulating mechanism90500), the retraction biasing member is permitted to expand in theproximal direction from its initial energized state. This axialexpansion in the proximal direction of the retraction biasing memberretracts the needle. If an inserter needle/trocar and cannulaconfiguration are utilized, retraction of the needle may occur whilemaintaining the cannula in fluid communication with the body of theuser. Accordingly, the insertion mechanism may be used to insert aneedle and cannula into the user and, subsequently, retract the needlewhile retaining the cannula in position for drug delivery to the body ofthe user.

As further discussed below, in some examples, the power and controlsystem 90800 and/or the drive control system 90820 may control theneedle insertion mechanism 90200 via the multi-function drive mechanism90100. Additionally, the power and control system 90800 and/or the drivecontrol system 90820 may control the rate of drug delivery via the drivemechanism 90100 and regulating mechanism 90500 such as by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer (thereby delivering drug substances at variable rates and/ordelivery profiles).

Referring back to FIGS. 70A-70D and 71A-71D, the multi-function drivemechanisms 90100 may concurrently or sequentially perform the steps of:triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a user; and connecting a sterile fluid pathway to adrug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user.

In at least one embodiment, as shown in FIGS. 70A-70D and 71A-71D, thecontrol unit 90810 may initiate motion of the actuator 90101 of thedrive control system 90820, which may cause rotation of the main/stargear 90102 of the multi-function drive mechanism 90100. Main/star gear90102 is shown as a compound gear with aspects 90102A and 90102B (seeFIG. 72). In one example, main/star gear 90102 conveys motion to theregulating mechanism 90500 through gear assembly 90516.

In another example, main/star gear 90102 conveys motion to the needleinsertion mechanism 90200 through gear 90112. As gear 90112 is rotatedby main/star gear 90102, gear 90112 engages the needle insertionmechanism 90200 to initiate the fluid pathway connector into the user,as described in detail above. In one particular embodiment, needleinsertion mechanism 90200 is a rotational needle insertion mechanism.Accordingly, gear 90112 is configured to engage a corresponding gearsurface 90208 of the needle insertion mechanism 90200 (see FIGS. 70A and71B). Rotation of gear 90112 causes rotation of needle insertionmechanism 90200 through the gear interaction between gear 90112 of thedrive mechanism 90100 and corresponding gear surface 90208 of the needleinsertion mechanism 90200. Once suitable rotation of the needleinsertion mechanism 90200 occurs, for example rotation along axis a′shown in FIG. 70B-70C, the needle insertion mechanism may be initiatedto create the fluid pathway connector into the user.

In an alternative embodiment, as shown in FIG. 75A, the insertionmechanism 90200 includes a rotationally biased member 90210 which isinitially held in an energized state. In one example, the rotationallybiased member is a torsional spring. The drive control system 90820 mayactuate one or more components of the multi-function drive mechanism90100, insertion mechanism 90200 and/or the regulating mechanism 90500to prevent and/or control the rotation of the rotational biasing member90210.

The gear 90112 may be configured to engage a corresponding gear surfaceof a control arm 90202 (visible in FIG. 75B) that contacts or blocks theneedle insertion mechanism 90200. Rotation of gear 90112 causes movementof the control arm 90202, which may initiate or permit rotation ofneedle insertion mechanism 90200.

Moreover, the rotational biasing member may be prevented fromde-energizing by contact of a component of the insertion mechanism witha rotation prevention feature, such as a blocking aspect of the controlarm, of the drug delivery device. In one example, the rotational biasingmember 90210 may be prevented from de-energizing by interaction of gearsurface 90208 with gear 90112.

It is contemplated that, in one example, at least the prevention of therotation of the rotational biasing member 90210 may be implemented priorto the on-body sensing. As such, when the on-body sensor 90840 sensesskin portion of the user, and/or the power and control system 90800receives input for initiation of the drug delivery (e.g., via theactivation button) and/or input for needle insertion, the power andcontrol system 90800 may command the drive control system 90820 topermit the rotationally biased member 90210 to, at least partially,de-energize. This may cause one or more components of the insertionmechanism 90200, drive control mechanism 90100 and/or regulatingmechanism 90500 to rotate and, in turn, cause, or allow, the insertionof the needle into the patient. Furthermore, a cannula may be insertedinto the patient as described above.

As detailed below, during the delivery of the drug, based on theinteractions among the drive control system 90820, the drive mechanism100 and the regulating mechanism 90500, the insertion mechanism may befurther controlled. For example, when the control arm or anothercomponent of the drive control system 90820 recognizes a slack in thetether, the rotationally biased member may be allowed to furtherde-energize, causing additional rotation of one or more components ofthe insertion mechanism 90200.

This rotation may cause, or allow, the drive control system 90820 toretract the needle from the patient. The needle may be fully retractedin a single step or there may be multiple steps of retraction.

In at least one embodiment, the needle insertion mechanism 90200 may beconfigured such that a particular degree of rotation upon rotationalaxis a′ (shown in FIGS. 70B-70C) enables the needle/trocar to retract asdetailed above. Additionally or alternatively, such needle/trocarretraction may be configured to occur upon a user-activity or uponmovement or function of another component of the drug delivery device.In at least one embodiment, needle/trocar retraction may be configuredto occur upon end-of-drug-delivery, as triggered by, for example, theregulating mechanism 90500 and/or one or more of the sensors (e.g., thetether sensor, pressure sensor, etc.) During these stages of operation,delivery of fluid substances from the drug chamber 9021 may beinitiated, on-going, and/or completed by the expansion of the biasingmember 90122 from its initial energized state acting upon the piston90110A, 90110B and plunger seal 9060.

Additionally or alternatively, the drive control system 90820 mayindirectly engage the needle insertion mechanism 90200 in order toestablish the sterile fluid connection sub-system 90300, as describedbelow.

VIII.B. Fluid Pathway Connector:

The power and control system 90800 and/or drive control system 90820 mayadditionally establish the fluid pathway connector or sub-system 90300by connecting the sterile fluid conduit to the drug container, to enablethe fluid pathway connector.

The establishment of the fluid pathway connector 90300 may be performedprior to, during, or after the wait time period. Additionally, thepathway connection 90300 may be established prior to, or during theactuation of the insertion mechanism 90200. In some embodiments, thepower and control system 90800 may cause the establishment of the fluidpathway connector 90300 via the multi-function drive mechanism 90100,and/or one of the other sub-systems such as the needle insertionmechanism or sub-system 90200. Generally, a suitable fluid pathwayconnector includes a sterile fluid conduit, a piercing member, and asterile sleeve attached to a drug container or a sliding pierceable sealintegrated within a drug container. The fluid pathway connector mayfurther include one or more flow restrictors. Upon activation of thedevice 9010, the fluid pathway connector 90300 is established to connectthe sterile fluid conduit 9030 to the drug container of the drivemechanism 90100. Such connection may be facilitated by a piercingmember, such as a needle, penetrating a pierceable seal of the drugcontainer of the drive mechanism 90100. The sterility of this connectionmay be maintained by performing the connection within a flexible sterilesleeve. Upon substantially simultaneous activation of the insertionmechanism 90200, the fluid pathway between drug container and insertionmechanism is complete to permit drug delivery into the body of the user.In one such embodiment, the fluid pathway connector may be substantiallysimilar to that described in International Patent Application No.PCT/US2012/054861, which is included by reference herein in its entiretyfor all purposes. In such an embodiment, a compressible sterile sleevemay be fixedly attached between the cap of the drug container and theconnection hub of the fluid pathway connector. The piercing member mayreside within the sterile sleeve until a connection between the fluidconnection pathway and the drug container is desired. The sterile sleevemay be sterilized to ensure the sterility of the piercing member and thefluid pathway prior to activation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Applications No.PCT/US2013/030478 or No. PCT/US2014/052329, for example, which areincluded by reference herein in their entirety for all purposes.

According to such an embodiment, a drug container 9050 may have a drugchamber 9021 within a barrel between a pierceable seal (not shown) and aplunger seal 9060. A drug fluid is contained in the drug chamber 9021.Upon activation of the device by the user, a drive mechanism (e.g.,multi-function drive mechanism 90100) asserts a force on a plunger seal9060 contained in the drug container. As the plunger seal 9060 asserts aforce on the drug fluid and any air/gas gap or bubble, a combination ofpneumatic and hydraulic pressure builds by compression of the air/gasand drug fluid and the force is relayed to the sliding pierceable seal.The pierceable seal is caused to slide towards the cap 9052, causing itto be pierced by the piercing member retained within the integratedsterile fluid pathway connector. Accordingly, the integrated sterilefluid pathway connector is connected (i.e., the fluid pathway is opened)by the combination pneumatic/hydraulic force of the air/gas and drugfluid within the drug chamber created by activation of a drive mechanism90100. Once the integrated sterile fluid pathway connector is connectedor opened, drug fluid is permitted to flow from the drug container 9050,through the integrated sterile fluid pathway connector 90300, sterilefluid conduit 9030, and insertion mechanism 90200, and into the body ofthe user for drug delivery. In at least one embodiment, the fluid flowsthrough only a manifold and a cannula and/or needle of the insertionmechanism, thereby maintaining the sterility of the fluid pathway beforeand during drug delivery.

In one embodiment, the power and control system 90800 may command thedrive control system 90820 to establish or activate the sterile fluidpathway subsystem or connection 90300. For example, the connection 90300may be established via the needle insertion mechanism 90200 which may beactivated or controlled by the multi-function drive mechanism 90100.

Additionally or alternatively, the sterile fluid pathway connector 90300may be directly initiated directly by the multi-function drive mechanism90100. For example, the control unit 90810 may command the motor 90101to actuate a rotational gear, such as the star gear 90102 described indetail herein, that may operate concurrently or sequentially to: (a)control the rate of drug delivery, (b) to actuate the needle insertionmechanism 90200, and/or (c) initiate the sterile fluid pathway connector90300, based on various predetermined times (e.g., the wait time period,the drug delivery period) as provided by the power and control system90800.

In one embodiment, shown in FIGS. 69A-69C, the multi-function drivemechanism 90100 performs all of these steps substantially concurrently.In that embodiment, the drive control system 90820 causes themulti-function drive mechanism 90100 to rotate a gear (e.g., star gear90102) that acts upon several other components (e.g., other gearassemblies). For example, the gear acts on a gear assembly to controlthe rate of drug delivery, while also contacting a needle insertionmechanism 90200 to introduce a fluid pathway connector 90200 into theuser. As the needle insertion mechanism 90200 is initiated, the sterilefluid connection is made to permit drug fluid flow from the drugcontainer 9050, through the fluid conduit 9030, into the needleinsertion mechanism 90200, for delivery into the patient as the gear andgear assembly of the multi-function drive mechanism control the rate ofdrug delivery.

It will be appreciated that, the drug delivery device 9010 is configuredto deliver a range of drugs with different viscosities and volumes viathe established sterile fluid pathway subsystem or connection 90300. Inaddition, the drug delivery device 9010 delivers a drug at a controlledflow rate (speed) and/or of a specified volume. In one embodiment, thedrug delivery process is controlled by one or more flow restrictors (notshown) within the fluid pathway connector and/or the sterile fluidconduit. In other embodiments, other flow rates may be provided byvarying the geometry of the fluid flow path or delivery conduit

As shown in FIGS. 70A-70D and 71A-71D, rotation of the needle insertionmechanism 90200 in this manner may also cause a connection of a sterilefluid pathway to a drug container to permit fluid flow from the drugcontainer to the needle insertion mechanism for delivery to the user. Insuch an example, the control unit 90810 may command and control: (a)drive mechanism 90100, (b) the needle insertion mechanism 200, and (c)the sterile fluid pathway connector 90300. For example, ramp aspect90222 of needle insertion mechanism 90200 is caused to bear upon amovable connection hub 90322 of the sterile fluid pathway connector90300. As the needle insertion mechanism 90200 is rotated by themulti-function drive mechanism 90100 (based on the control unit 90810command), ramp aspect 90222 of needle insertion mechanism 90200 bearsupon and translates movable connection hub 90322 of the sterile fluidpathway connector 90300 to facilitate a fluid connection therein. Suchtranslation may occur, for example, in the direction of the hollow arrowalong axis ‘C’ shown in FIGS. 70B and 71B.

Moreover, the drug delivery device 9010 may control the flow rate of thedrug. In one example, the flow rate may be controlled by the drivecontrol system 90820 (e.g., the motor of the drive control system) byvarying the speed at which one or more components of the drive mechanism90100 advances into the drug container 9050 to dispense the drug. It isnoted that, a combination of the different flow rate control methods maybe implemented to control the flow of the drug via the sterile fluidpathway connector 90300.

The power and control system 90800 (e.g., the control unit 90810) maysend command signal to the drive control system 90820 to control theflow rate control sub-system or regulating mechanism 90500 via themultifunction drive mechanism 90100 as discussed below. The rate of drugdelivery as controlled by the drive control system 90820 may bedetermined by: selection of the gear ratio of gear assembly 90516;selection of the main/star gear 90102; selection of the diameter ofwinding drum/gear 90520 and further driving such elements by commandingthe actuator 90101 to control the rate of rotation of the main/star gear90102; or any other method known to one skilled in the art. By usingelectromechanical actuator 90101 to control and adjust the rate ofrotation of the main/star gear 90102, it may be possible to configurethe drug delivery device 9010 to provide a variable dose rate (i.e., therate of drug delivery is varied during a treatment).

Additionally, the drive control system 90820 may control the regulatingmechanism or sub-system 90500 which may include controlling the rate ofdrug delivery by metering, providing resistance, or otherwise preventingfree axial translation of the plunger seal utilized to force a drugsubstance out of a drug container.

With references to the embodiments shown in FIGS. 70A-70D and 71A-71D,the power and control system 90820 may control the drive mechanism 90100via the motor 90101. The drive mechanism 90100 may include a gearassembly 90110 including a main gear 90102, a drive housing 130, and adrug container 9050 having a cap 9052, a pierceable seal (not visible),a barrel 9058, and a plunger seal 9060. The main gear 90102 may be, forexample, a star gear disposed to contact multiple secondary gears orgear surfaces. A drug chamber 9021, located within the barrel 9058between the pierceable seal and the plunger seal 9060, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. The seals described hereinmay be comprised of a number of materials but are, in a preferredembodiment, comprised of one or more elastomers or rubbers. The drivemechanism 90100 may further contain one or more drive biasing members,one or more release mechanisms, and one or more guides, as are describedfurther herein. The components of the drive mechanism 90100 function toforce a fluid from the drug container out through the pierceable seal,or preferably through the piercing member of the fluid pathway connector90300, for delivery through the fluid pathway connector, sterile fluidconduit, and insertion mechanism into the body of the user.

In one particular embodiment, the drive mechanism 90100 employs one ormore compression springs as the drive biasing member(s) 90122. In suchembodiment, upon the activation of the drug delivery device by the user(e.g., via the activation button) the power and control system 90800 maybe configured to directly or indirectly (and electromechanically)release the drive biasing members 90122 from an energized state. Uponrelease, the drive biasing members 90122 may bear against and act uponthe plunger seal 9060 to force the fluid drug out of the drug container.The compression spring may bear against and act upon a piston which, inturn, acts upon the plunger seal 9060 to force the fluid drug out of thedrug container. In one example, one or more drive biasing members 90122may be compressed between the drive housing 90130 and piston 90110,wherein the drive biasing members 90122 may bear upon an interfacesurface 90110C of the piston.

Optionally, a cover sleeve (not shown) may be utilized between the drivebiasing members 90122 and the interface surface 90110C of the piston90110 for example, to promote even distribution of force from the drivebiasing member 90122 to the piston 90110, prevent buckling of the drivebiasing members 90122, and/or hide biasing members 90122 from user view.Interface surface 90110C of piston 90110 is caused to rest substantiallyadjacent to, or in contact with, a proximal end of seal 9060. Althoughthe embodiments shown in FIGS. 70A-70D and 71A-71D show a singularbiasing member it is also contemplated that one or more biasing membersdisposed to act in parallel may be used.

As discussed below, in some embodiments, the drive control system 90820and/or the power and control system 90800 may control the delivery rateof the drug via the drive mechanism 90100, insertion mechanism 90200 andthe regulating mechanism 90500.

As best shown in FIG. 70D and FIG. 71D, the piston 90110 may becomprised of two components 90110A and 90110B and have an interfacesurface 90110C to contact the plunger seal 9060.

Moreover, a tether, ribbon, string, or other retention strap (referredto herein as the “tether” 90525) may be connected at one end to thepiston 90110A, 90110B. For example, the tether 90525 may be connected tothe piston 90110A, 90110B by retention between the two components of thepiston 90110A, 90110B when assembled. The tether 90525 is connected atanother end to a winch drum/gear 90520 of regulating control mechanism90500. Through the use of the winch drum/gear 90520 connected to one endof the tether 90525, and the tether 90525 connected at another end tothe piston 90110A, 90110B, the regulating mechanism 90500 functions tocontrol, meter, provide resistance, or otherwise prevent free axialtranslation of the piston 90110A, 90110B and plunger seal 9060 utilizedto force a drug substance out of a drug container 9050.

Accordingly, the power and control system 90800 may control theregulating sub-system or mechanism 90500 which may be a portion of thegear assembly 90116 aspect of the multi-function drive mechanism, andwhich together may function to control the rate or profile of drugdelivery to the user.

With reference to FIG. 76C, the power and control system, via the drivecontrol system 90820, may control the regulating mechanism 500 (e.g.,via the drive control mechanism 90100). For example, the control unit90810 may drive the actuator or Pac-Man motor 90101 to drive variousgear assembly (e.g., gear assembly 90516) of the regulating mechanism90500, by selecting appropriate configurations for the motor 90101 andgear assembly. Moreover, the driving of the regulating mechanism may betime-controlled, as discussed herein.

As shown in FIGS. 70A-70D and 71A-71D, and in isolation in FIGS. 72 and73A-73B, in the embodiments of the present disclosure, the regulatingmechanism 90500 is gear assembly driven by an actuator 90101. Moreover,upon receiving command signals from the control unit 90810, the motor90101 may control the regulating mechanism 90500 to retard or restrainthe distribution of tether 90525, thus allowing the tether 90525 toadvance at a regulated or desired rate. This restricts movement ofpiston 90110 within barrel 9058, which is pushed by one or more biasingmembers 90122, hence controlling the movement of plunger seal 9060 anddelivery of the drug contained in chamber 9021. As the plunger seal 9060advances in the drug container 9050, the drug substance is dispensedthrough the sterile pathway connection 90300, conduit 9030, insertionmechanism 90200, and into the body of the user for drug delivery. In oneexample, the regulated motion of the tether 90525 may be monitored by anoptional tether sensor 90875 which may provide status feedback to thecontrol unit 90810 of the power and control system 90800. The controlunit 90810 may process the feedback status information of the regulatedmotion of the tether 90525 to further control the regulating mechanism90500.

As discussed above, in at least one embodiment, the motor 90101 may be aPac-Man motor that has a gear interface within which one or more teethof the main gear may partially reside during operation of the drugdelivery pump device 9010. The operation of the Pac-Man motor may becontrolled by the control unit 90810. (see FIGS. 73A-73B).

In one example, when the gear interface 90101A of the Pac-Man motor90101 is in alignment with a tooth 90102A of the main gear 90102,rotational motion of the Pac-Man motor 90101 causes gear interfacerotation of the main gear 90102. When the Pac-Man motor 90101 is betweengear teeth of the main gear, it may act as a resistance for, forexample, back-spinning or unwinding of the gear assembly 90116. In oneparticular embodiment, the Pac-Man motor 90101 utilizes an alternatingdirection type motor to rotate the Pac-Man motor 90101 backwards andforwards. This configuration aids in the prevention of a runawaycondition, where the motor and the gears are freely permitted to rotate,by using the multi-direction of the motor to prevent continuous spin inone direction (as would be needed for a runaway condition). Thisbi-directional movement of the motor, coupled with the use of the gearinterface cut within the Pac-Man motor, may provide suitable safetyfeatures to prevent a runaway condition that could potentially lead toover-delivery of drug to the user. Further detail about the gearassembly 90116, regulating mechanism 90500, and multi-function drivemechanism 90100 are provided herein. In a particular embodiment shown inFIGS. 73A-73B, the regulating mechanism 90500 further includes one ormore gears 90511, 90512, 90513, 90514, of a gear assembly 90516. One ormore of the gears 90511, 90512, 90513, 90514 may be, for example,compound gears having a small diameter gear attached at a shared centerpoint to a large diameter gear. Gear 90513 may be rotationally coupledto winch drum/gear 90520, for example by a keyed shaft, thereby couplingrotation of gear assembly 90516 to winch drum/gear 90520. Compound gear90512 engages the small diameter gear 90513 such that rotationalmovement of the compound gear aspect 90512B is conveyed by engagement ofthe gears (such as by engagement of corresponding gear teeth) to gear90513. Compound gear aspect 90512A, the rotation of which is coupled togear aspect 90512B, is caused to rotate by action of compound gearaspect 102B of the main/star gear 90102. Compound gear aspect 90102B,the rotation of which is coupled to main/star gear 90102, is caused torotate by interaction between main/star gear 90102A and interface 90101Aof the actuator 90101. Thus, rotation of main/star gear 90102 isconveyed to winch drum/gear 90520. Accordingly, rotation of the gearassembly 90516 initiated by the actuator 90101 (of the drive controlsystem 90820) may be coupled to winch drum/gear 90520 (i.e., through thegear assembly 90516), thereby controlling the distribution of tether90525, and the rate of movement of plunger seal 9060 within barrel 9058to force a fluid from drug chamber 9021. The rotational movement of thewinch drum/gear 90520, and thus the axial translation of the piston90110 and plunger seal 9060, are metered, restrained, or otherwiseprevented from free axial translation by other components of theregulating element 90500, as described herein. As described above, theactuator 90101 may be a number of known power/motion sources including,for example, a motor (e.g., a DC motor, AC motor, or stepper motor) or asolenoid (e.g., linear solenoid, rotary solenoid).

As discussed above, the embodiments shown in FIGS. 75A-75B show anactuator 90101 that is driven by the control unit 90810, and is inhorizontal alignment and indirect engagement with the main/star gear90102. Such an embodiment may utilize a rack and pinion engagement, adrive screw, or a worm gear 90101W, as shown in FIGS. 75A-75B, to changethe direction of motion from horizontal to vertical (i.e., perpendicularinteraction). Actuator 90101 (based on command signals received from thecontrol unit 90810) rotates worm gear 90101W, which engages gear 90101Gand conveys the motion to the Pac-Man gear 90101A. The Pac-Man gear90101A engages main/star gear 90102 to enable operation of the drivemechanism and the drug delivery device, as described herein.

The control unit 90810 controls main star gear 90102 via the motor90101. The main star gear 90102 may then drive other gear assembly. Forexample, main/star gear 90102 may drive operation of gear 90112 toenable operation of the needle insertion mechanism 90200, as describedherein.

In one embodiment, the control unit 90810 provides command signals suchthat the actuator 90101 rotate the worm gear 90101W, gear 90101G, andPac-Man gear 90101A backwards and forwards. This configuration aids inthe prevention of a runaway condition, where the motor and the gears arefreely permitted to rotate, by using the multi-direction of the motor toprevent continuous spin in one direction (as would be needed for arunaway condition). This bi-directional movement of the actuator 90101,coupled with the use of the gear interface of the worm gear 90101W, gear90101G, and Pac-Man gear 90101A with the main/star gear 90102, providesuitable safety features to prevent a runaway condition that couldpotentially lead to over-delivery of drug to the user.

Additionally, the motor 90101 may include a stop member 90101B thatstops the rotation of the Pac-Man gear 90101A against a stop block90150. Stop block 90150 further prevents over-rotation of the Pac-Mangear 90101A and, accordingly, the main/star gear 90102 to prevent arunaway condition that could potentially lead to over-delivery of drugto the user. For the device to function in this configuration, thePac-Man gear 90101A must be rotated backwards the other direction beforerotating forwards again to progress the main/star gear 90102 because thestop member 90101B prevents over rotation in one direction byinteraction with the stop block 90150.

Additionally, the geometry of worm gear 90101W may be configured suchthat it is self-locking and/or cannot be back-driven by gear 90101G.This may be done by configuration of parameters such as: pitch, leadangle, pressure angle, and number of threads. In so doing, runawayconditions of the drive mechanism will be prevented by the worm gear'sresistance to rotations that are not caused by actuator 90101.Alternatively or additionally, the control unit 90810 may be configuredto determine whether there is any feedback from the worm gear 90101Wthat is caused by the rotations of other gears (e.g., gear 90101G) andnot by the motor 90101. If the control unit 90810 determines or receivessuch feedback, the control unit 90810 may terminate further operations.

It is noted that, the power and control system 90800 does not controlthe regulating mechanisms 90500 of the present disclosure to drive thedelivery of fluid substances from the drug chamber 9021. The delivery offluid substances from the drug chamber 9021 is caused by the expansionof the biasing member 90122 from its initial energized state acting uponthe piston 90110A, 90110B and plunger seal 9060 (which may be actuatedby the control unit 90810 via the motor 101). The regulating mechanisms90500 instead function to provide resistance to the free motion of thepiston 90110A, 90110B and plunger seal 9060 as they are pushed by theexpansion of the biasing member 90122 from its initial energized state.The regulating mechanism 90500 does not drive the delivery but onlycontrols the delivery motion. The tether limits or otherwise restrainsthe motion of the piston 90110 and plunger seal 9060, but does not applythe force for the delivery. According to a preferred embodiment, thecontrolled delivery drive mechanisms and drug delivery devices of thepresent disclosure include a regulating mechanism indirectly or directlyconnected to a tether metering the axial translation of the piston90110A, 90110B and plunger seal 9060, which are being driven to axiallytranslate by the biasing member 90122.

In one example, the power and control system 90800 of the drug deliverydevice 9010 may be configured to receive one or more regulatingparameters for controlling the regulating mechanism 90500.Alternatively, or additionally the power and control system 90800 mayreceive sensor inputs (e.g., heart rate sensor, glucose monitor sensorinformation) and may then translate the sensor inputs into regulatingparameters. The control unit 90810 may then control the regulatingmechanism 90500 after a predetermined time (e.g., after the wait timeperiod). Based on the inputs, the control unit 90810 may meter therelease of the tether 90525 by the winch drum/gear 90520 and therebypermit axial translation of the piston 90110 by the biasing member 90122to translate a plunger seal 9060 within a barrel 9058.

Based on the regulating parameters, the control unit 90810 and motor90101 may additionally control the restraint provided by the tether90525 and winch drum/gear 90520 on the free axial translation of thepiston 90110 upon which the biasing member 90122 bears upon via themotor 90101. The control unit 90810 may control such operations toprovide a desired drug delivery rate or profile, to change the dosevolume for delivery to the user, and/or to otherwise start, stop, orpause operation of the drive mechanism. In one example, the control unit90810 may control the drug delivery rate in order to complete a drugdelivery dose within a desired or a predetermined time.

During the drug delivery process, and after a predetermined wait timeperiod, the power and control system may provide delivery instructionsto the drive control system 90820. Based on the instructions, the drivecontrol system may control the components of the drive mechanism 90100,to axially translate the plunger seal 9060 of the drug container 9050 inthe distal direction. Optionally, the drive mechanism 90100 and/or theregulating mechanism 90500 may include one or more compliance featureswhich enable additional axial translation of the plunger seal 9060 to,for example, ensure that substantially the entire drug dose has beendelivered to the user. For example, the plunger seal 9060, itself, mayhave some compressibility permitting a compliance push of drug fluidfrom the drug container.

For example, the controlled delivery drive mechanisms and/or drugdelivery devices of the present disclosure may additionally enable acompliance push to ensure that substantially all of the drug substancehas been pushed out of the drug chamber 9021. The plunger seal 9060,itself, may have some compressibility permitting a compliance push ofdrug fluid from the drug container. For example, when a pop-out plungerseal is employed, i.e., a plunger seal that is deformable from aninitial state, the plunger seal may be caused to deform or “pop-out” toprovide a compliance push of drug fluid from the drug container.Additionally or alternatively, an electromechanical status switch may beutilized to contact, connect, or otherwise enable a transmission to thecontrol unit 90810 of the power and control system 90800 to signalend-of-dose to the user. This configuration may further enable trueend-of-dose indication to the user.

As discussed with reference to FIG. 76B, the drive control system 90820may include various sensors (e.g., the tether sensor 90875, valve sensor90877, pressure sensor 90870) that may be coupled to the control unit90810 and/or to the motor 90101. The sensors may be configured toprovide signal or status information for various elements of the systemsand sub-systems of the drug delivery device 9010. In one example, thecontrol unit 90810 may process the feedback signals or the statusinformation received from the sensors to control the sub-systems, suchas the regulating sub-system or mechanism 90500.

Additionally, the power and control system 90800 may providenotification to the user based on the feedback provided by the sensorsto the control unit. The notification may be tactile, visual, and/orauditory, as described above, and may be redundant such that more thanone signal or type of notification is provided to the user during use ofthe device. For example, the user may be provided an initialnotification to indicate that the drug delivery device 9010 isoperational and ready for drug delivery and may further may provide anend-of-dose notification, based on the feedback signal provided, forexample, by one or more sensors. In one example, pressure sensor 90870and/or a valve sensor 90877, positioned at appropriate location in thedrug delivery device 9010, may sense the end-of-dose when the pistonreaches the end of its axial translation. Accordingly, the control unit90810 may then provide an end-of-dose notification based on the sensorsignals received from the sensors.

Additionally or alternatively, tether 90525 may have one or more sensortriggers such as electrical contacts, optical markings, and/orelectromechanical pins or recesses that are configured to provide statusfeedback to the tether sensors 90875, and in turn, to the control unit90820. In at least one embodiment, an end-of-dose status notificationmay be provided to the user once the tether sensor 90875 detects thatthe final status trigger positioned on the tether 90525 has reached afinal position upon the end of axial travel of the piston 90110A, 90110Band plunger 9060 within the barrel 9058 of the drug container 9050. Thetether sensor 90875 may be, for example, an electrical switch reader tocontact the corresponding electrical contacts, an optical reader torecognize the corresponding optical markings, or a mechanical orelectromechanical reader configured to contact corresponding pins,holes, or similar aspects on the tether 90525.

In one example, the status triggers (not shown) may be positioned alongthe tether 90525 to be read or detected at positions which correspondwith the beginning and end of drug delivery, as well as at desiredincrements during drug delivery.

In some examples, the drive control system 90820 initiates the drugdelivery (upon actuation of the drive mechanism 90100) by release of thebiasing member 90122 and the resulting force applied to the piston90110A, 90110B and plunger seal 9060. The power and control system 90800further instructs the drive control system 90820 to control the rate orprofile of drug delivery to the user by controlling the regulatingmechanism 90500, gear assembly 90516, winch drum/gear 90520, releasingthe tether 90525 and permitting expansion of the biasing member 90122and axial translation of the piston 90110A, 90110B and plunger seal9060. As this occurs, the status triggers of the tether 90525 arecontacted or recognized by the tether sensor and the status of the drivemechanism before, during, and after operation can then be relayed to thecontrol unit 90810 of the power and control system 90800 to providefeedback to the user. Depending on the number of status triggers locatedon the tether 90525, the frequency of the incremental status indicationmay be varied as desired. As described above, a range of tether sensorsmay be utilized depending on the status triggers utilized.

In some embodiments, the tether sensor may include one or more sensorsof similar type, and/or a combination of different types of sensors. Inone example, a tension force may be applied to the tether 90525 (e.g.,according to one or more command signals from the control unit 90810).When the drug delivery device 9010 reaches the end-of-dose, the tether90525 goes slack which may be detected by a tether sensor 90875 such asan electrical or electromechanical switch. The tether sensor 90875 maysignal a slack in the tether 90525 to the control unit 90810 of thepower and control system 90800.

Additionally, gear 90511A and/or gear 90511B of gear assembly 90516 maybe configured as an encoder along with a sensor. For example, thesensor/encoder combination may be configured to provide feedback of gearassembly rotation. In one example, the encoder/sensor may be calibratedto an initial position of the piston (e.g., the position of piston 90110when there is no slack in the tether 90525). Moreover, this positionalinformation may be recorded or stored in the control unit 90810. Assuch, the control unit 90810 or the power and control system 800 mayreceive positional feedback, end-of-dose signal, and error indication,such as an occlusion, for example, due to a slack in the tether 90525prior to reaching the expected number of motor rotations as counted bythe sensor/encoder. Alternatively or additionally, the drive controlsystem 90820 may control the rate of flow of drug via the tether 90525in combination with the regulating mechanism 90500.

It will be appreciated that, additional and/or alternative means may beimplemented for terminating or restraining the flow of the medicament inthe case of slack in, or failure of, the tether 90525 (e.g., during abreakage of the tether).

FIGS. 74A-74B shows one such embodiment for a safety-stop during afailure of the tether 90525. Disposed within barrel 9058 are brake 9064,sleeve 9062, and plug 9068, and optionally retainer 9066. Biasing member90122 bears against sleeve 9062. Initially, the tether 90525 is engagedwith plug 9068, thereby allowing tether 90525 to restrain the motion ofsleeve 9062. This restraint controls the rate of expansion orde-energizing of biasing member 90122. When tether 90525 is undertension, plug 9068 bears against distal face 9064A of brake 9064,causing proximal face 9064B of brake 9064 to bear against sleeve 9062.Due to this contact, and the profile of the distal end 9062A of sleeve9062, brake 9064 is maintained in a substantially conical configurationas shown in FIG. 74A. In this configuration, expansion or de-energizingof biasing member 90122 is restrained. Also, in this conicalconfiguration, the outer diameter of brake 9064 is less than the innerdiameter of barrel 9058, thus translation of the brake is not restrainedby contact with the inner wall of the drug container. Also, a portion ofbrake 64 is in contact with retainer 9066. Because brake 9064 ismaintained in this configuration by plug 9068 and sleeve 9062,translation of sleeve 9062, caused by decompression of biasing member90122, is transferred to retainer 9066. Likewise, contact of retainer9066 with plunger seal 9060 causes translation of plunger seal 9060.

As shown in FIG. 74B, in the event of slack in, or failure of, tether90525, plug 9068 is no longer held in position by tether 90525 and,therefore, no longer restrains motion of sleeve 9062. As biasing member90122 decompresses or de-energizes, brake 9064 transforms to arelatively less conical or flatter configuration. This may be caused bya natural bias of brake 9064 to transform to this configuration or,alternatively, may be caused by contact of brake 9064 with both retainer9066 and sleeve 9062. As the brake is transformed, it comes into contactwith the inner wall of barrel 9058. The brake thus acts as a wedge torestrict translation of sleeve 9062. This may prevent furthertranslation or may act to restrict the rate of translation. Optionally,restoring tension in the tether may cause the plug to contact the brakeand to transform the brake back to its conical configuration and thusrestore normal operation of the drug delivery device.

FIGS. 74A-74B shows the plug as having a spherical shape and the brakeas having a conical shape. Such shapes are used herein merely forexemplary purposes and other shapes or configurations could readily beutilized to achieve the same or similar functionality. For example, theplug may itself be conical in shape and, in one embodiment, be shaped tointerface the brake when the brake is in a conical shape. In such aconfiguration, the conical shape of the plug assists in maintaining theconical shape of the brake, thereby preventing contact between the outerdiameter of the brake with the inner diameter of the barrel in order torestrict the axial translation of the sleeve 9062 (i.e., applying abraking force). In another embodiment, the brake 9064 could employ astar-shaped or other configuration when in a substantially flattenedposition so as to make contact with the inner diameter of the barrel9058 to prevent or restrict further axial translation of sleeve 9062.Without further translation of sleeve 9062, biasing member 90122 cannotexpand or de-energize further which, in turn, prevents or restrictsfurther drug delivery to the user. This provides a necessary and usefulsafety measure for drug delivery, to prevent over-delivery oraccelerated delivery of drug to the user.

Moreover, as discussed above, the control of the tether 90525 may beprovided by the control unit 90810. Additionally, any feedback relatedto slack or failure of the tether 90525 may be provided to the drivecontrol system 90820 and/or to the power and control system 90800.

As described above, the regulating mechanisms 90500 provide resistanceto the free motion of the piston 90110A, 90110B and plunger seal 9060 asthey are pushed by the expansion of the biasing member 90122 from itsinitial energized state. The regulating mechanism 90500 may not drivethe delivery but may only control the delivery motion.

It is noted that, the tether may limit or restrain the motion of thepiston 90110 and plunger seal 9060, but may not apply the force for thedelivery (see FIGS. 70A-70D and 71A-71D). The motion of the piston90110A, 90110B and plunger seal 9060 as they are pushed by the expansionof the biasing member 90122 from its initial energized state are shownin the direction of the solid arrow along axis ‘A’ from proximal orfirst position ‘P’ to the distal or second position ‘D’, as shown in thetransition of FIGS. 70A-70D and 71A-71D.

Control of the tether 90525 is further described with reference to FIG.72 and FIGS. 73A-73B.

FIG. 72 shows a perspective view of the multi-function drive mechanism,according to at least a first embodiment, during its initial lockedstage. Initially, the tether 90525 may retain the biasing member 90122in an initial energized position within piston 90110A, 90110B. When thepower and control system 90800 receives inputs for activation, itcommands the drive control system to initiate the multi-function drivemechanism 90100. In one example, the drive mechanism 90100 may cause thebiasing member to impart a force to piston 90110 and therefore to tether90525. This force on tether 90525 imparts a torque on winding drum 90520which causes the gear assembly 90516 and regulating mechanism 90500 tobegin motion.

Moreover, as shown in FIG. 71C, the piston 90110 and biasing member90122 are both initially in a compressed, energized state behind theplunger seal 9060. The biasing member 90122 may be maintained in thisstate until activation of the device between internal features of drivehousing 90130 and interface surface 90110C of piston 90110A, 90110B. Asthe drug delivery device 9010 is activated and the drive mechanism 90100is triggered to operate, biasing member 90122 is permitted to expand(i.e., decompress) axially in the distal direction (i.e., in thedirection of the solid arrow shown in FIGS. 70A-70D and FIGS. 71A-71D).Such expansion causes the biasing member 90122 to act upon and distallytranslate interface surface 90110C and piston 90110, thereby distallytranslating plunger seal 9060 to push drug fluid out of the drug chamber9021 of barrel 9058.

As discussed above, an end-of-dose status indication may also beprovided to the user once one or more sensors contacts or detects theend of axial travel of the piston 90110A, 90110B and plunger seal 9060within the barrel 9058 of the drug container 9050 (e.g., based on astatus trigger positioned on the tether 90525). The status triggers maybe positioned along the tether 90525 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the user. In at least one embodiment,the sensor is an optical status reader configured to recognize thecorresponding optical status triggers on the tether. As would beunderstood by an ordinarily skilled artisan, such optical statustriggers may be markings which are recognizable by the optical statusreader. In another embodiment, the status reader is a mechanical orelectromechanical reader configured to physically contact correspondingpins, holes, or similar aspects on the tether. Electrical contacts couldsimilarly be utilized on the tether as status triggers which contact orare otherwise recognized by the corresponding electrical sensors. Thestatus triggers may be positioned along the tether 90525 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asshown, tether 90525 passes substantially axially through the drivemechanism housing 90130, the biasing member 90122, and connects to thepiston 90110 A, 90110B to restrict the axial translation of the piston90110A, 90110B and the plunger seal 9060 that resides adjacent thereto.The sensors may communicate the detected information (e.g., the end ofdose information, incremental motion, restricted motion, etc.) to thedrive control system 90820 and/or to the power and control system 90800to notify or provide feedback of the controlled motion of the variouscomponents.

As mentioned above various sensors may be coupled directly to the powerand control system 800 or via the drive control system 90820, and may beconfigured to provide the incremental status indication. A user may thenbe notified of such indication based on, for example, the detection ofthe rotational movement of one or more gears of gear assembly 90516. Forexample, as the gear assembly 90516 rotates, a sensor may read or detectone or more corresponding status triggers on one of the gears in thegear assembly to provide incremental status indication before, during,and after operation of the variable rate controlled delivery drivemechanism. A number of sensors may be utilized within the embodiments ofthe present disclosure.

In one example, the drive mechanism 90100 may utilize anelectro-mechanical sensor which may be physically in contact with thegear teeth of one of the gears of the gear assembly. As the sensor iscontacted by the status or sensor trigger(s), which in this exemplaryembodiment may be the gear teeth of one of the gears (or holes, pins,ridges, markings, electrical contacts, or the like, upon the gear), thesensor measures or detects the rotational position of the gear andtransmits a signal to the power and control system 90800 for statusindication or notification to the user.

Additionally or alternatively, the drive mechanism 90100 may utilize anelectro-optical sensor. The optical sensor may include a light beam thatmay be configured detect a motion and transmit a status signal to thepower and control system. For example, the optical sensor may beconfigured to detect motion of the gear teeth of one of the gears in thegear assembly (or holes, pins, ridges, markings, electrical contacts, orthe like, upon the gear). In another embodiment, the sensor may be anelectrical switch configured to recognize electrical contacts on thegear. In any of these embodiments, the sensor may be utilized to thentransmit a signal to the power and control system to providenotification feedback to the user about the controlled motion and/or thedelivery of the drug.

As would be appreciated by one having ordinary skill in the art,electro-optical sensors and corresponding triggers, electromechanicalsensors and corresponding triggers, and/or electrical or mechanicalsensor and corresponding triggers may all be implemented by theembodiments of the present disclosure to provide incremental statusindication to the user power and control system 90800. While the drivemechanisms of the present disclosure are described with reference to thegear assembly and regulating mechanism, a range of configurations may beacceptable and capable of being employed within the embodiments of thepresent disclosure, as would readily be appreciated by an ordinarilyskilled artisan. Accordingly, the embodiments of the present disclosureare not limited to the specific gear assembly and regulating mechanismdescribed herein, which is provided as an exemplary embodiment of suchmechanisms for employment within the controlled delivery drivemechanisms and drug delivery pumps.

Moreover, in at least one embodiment of the present disclosure, thedelivery profile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of actuator 90101. The change in the rate of movementof actuator 90101 causes a change in the rotation rate of regulatingmechanism 500 which, in turn, controls the rate of drug delivery to theuser. Alternatively, the delivery profile may be altered by a change inthe characteristics of the flow path of medicament through the conduitconnecting the drug container and insertion mechanism. The change may becaused by the introduction, removal, or modification of a flowrestrictor which restricts flow of medicament from the drug container tothe insertion mechanism. For example, a flow restrictor may havemultiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

Details of an exemplary method associated with drug delivery in apredetermined time are now provided with references to FIG. 9A. One ormore steps of the method 90900 may be executed during active power modeor non-active power mode of the power and control system 90800. Themethod 90900, for example, includes steps related to initiating anddelivering drug at an adjusted rate to a user by a drug delivery device9010 after a predetermined wait time period. The method includes stepsof communication between the drug delivery device 9010 and a mobiledevice 9011. The method may optionally monitor and receive information(e.g., heart rate of the user, glucose/insulin information, etc.)related to the health of the patient during the monitoring period.Particularly, the method requests a user of the drug delivery device9010 to activate the needle insertion (i.e., initiate NIM 90200), afterthe device has been activated. When the needle insertion has beenactuated, the drug delivery device 9010 may then initiate a timer totrack delay time period. Alternatively, a timer may be initiated by theactivation of the device.

Furthermore, the method determines whether the predetermined wait timeperiod has elapsed, and based on the determination notifies the useraccordingly about the initiation of the drug delivery process. Themethod regulates the delivery rate of the drug based on informationreceived from sensors (e.g., temperature sensor, heart rate sensor,glucose monitor sensor). Regulation of the delivery rate may be based onoptimization of the effectiveness of the drug. Alternatively, oradditionally, the delivery rate may be regulated to reduce and/orminimize the user's discomfort. For example, delivery of a relativelycold drug may cause pain to the user. Hence, if the temperature sensorprovides a signal to the control unit that the drug and/or drugcontainer is low, the delivery rate may be reduced.

The method may further determine whether the drug delivery has ended,and based on the determination, in one example may further transmit theend of drug delivery information to the mobile device. The mobile devicemay further provide the received information to a remote server (e.g., acloud server). Other parameters may be regulated based on the inputsfrom the sensors. For example, the delay between activation of anend-of-dose sensor and notification, to the user, that drug delivery hascompleted. The viscosity of the drug may be dependent on the temperatureof the drug and a more viscous drug may require additional time to befully delivered to the user. Hence, the control unit may use the inputfrom the temperature sensor to determine how long to delay notificationto the user of completion of delivery. The control unit may, forexample, compare the input from the temperature sensor to a look-uptable which is either stored locally or is accessed remotely.Alternatively, the control unit may use the input from the temperaturesensor as an input in an equation used to calculate the delay.

Referring now to FIG. 77A, the process flows depicted are merelyembodiments of the disclosure and are not intended to limit the scope ofthe disclosure. For example, the steps recited in any of the method orprocess descriptions may be executed in any order and are not limited tothe order presented. Furthermore, it will be appreciated that thefollowing description makes appropriate references not only to the stepsdepicted in FIG. 77A, but also to the various system components asdescribed with reference to the present disclosure.

Referring now to FIG. 77A, at step 90901, the pump device 9010 isactivated. The drug delivery device 9010 may be configured with anactivation mechanism that may include receiving a trigger signal fromthe user to power the power and control system 90800. In one example, auser may activate the drug delivery device 9010 by pressing a startbutton that may be an on/off switch, and/or a toggle switch. Theactivation button or the switch may be located through the pump housing9012, such as through an aperture between upper housing and lowerhousing, and which contacts either directly or indirectly the power andcontrol system 90800 (e.g., a via electrical contacts). The user maypress the activation button or the switch a predetermined number oftimes (e.g., one single press) to initially activate the drug deliverydevice 9010. Alternatively, the pump device 9010 may be configured suchthat it is activated upon removal from a portion of its packaging. Thepump device 9010 may include one or more packaging status sensors thatare configured to detect the removal of the pump device from a portionof the packaging. The packaging status sensor may take any form capableof detecting a removal of the pump device from a portion of thepackaging. For example, the packaging status sensor may be in the formof a pin interconnect on the power and control system 800 that is eitherconnected or disconnected when packaged. Removal from the packaging maycause the pin interconnect to change state from connected todisconnected or vice versa. This change of state may cause initiation ofthe timer. Alternatively, the packaging status sensor may consist of anoptical sensor which is configured to detect a change in lightingconditions caused by a removal of the pump device 9010 from a portion ofthe packaging.

In one example, upon receiving the activation input, a short-rangewireless communication link may be initiated between the drug deliverydevice 9010 and the mobile device 9011. In one example, the wirelesscommunication link may be established based on a Bluetooth pairingbetween the mobile device 9011 and the drug delivery device 9010.

In one example, during and/or upon the activation, the drug deliverydevice 9010 may be in a discovery mode, during which the mobile device9011 may discover the drug delivery device 9010, and establish thewireless communication with the drug delivery device 9010.Alternatively, the drug delivery device 9010 may initiate and establishthe wireless communication with the mobile device 9011 by sendingshort-burst signals or pings to the mobile device 9011.

Upon receiving the activation signal, the pump device 9010 may providenotification or feedback to the user to indicate that the device 9010has been activated. For example, notification signals, such as audibletones, and/or visual notification such as LED lights, may be provided bythe power and control system 90800.

It is contemplated that, in one example, a user may use the mobiledevice 9011 to activate the drug delivery device 9010. In such anexample, prior to activation, the drug delivery device 9010 may be incommunication only mode during which the drug delivery device 9010 maybe configured to establish a communication link with the mobile device9011 (e.g., Bluetooth pairing). Upon establishing the communication linkbetween the two devices, the user may select or press activation/startbutton 9010 b to activate the drug delivery device 9010.

In one example, the housing 9012 may include one or more statusindicators (e.g., light emitting diodes (LEDs) and/or speakers) andwindows that may provide indication of the activation of the drugdelivery device 9010. The activation mechanism, the status indicator,the window, and combinations thereof may be provided on the upperhousing or the lower housing such as, for example, on a side visible tothe user when the drug delivery device 9010 is placed on the body of theuser. Housing 9012 is described in further detail hereinafter withreference to other components and embodiments of the present disclosure.

Additionally or alternatively, the drug delivery device 9010 may pushthe activation notification to the mobile device 9011. In this example,the mobile app 9010 a may cause the mobile device 9011 to provide thenotification via speakers or LED lights (not shown) of the mobile device9011. Alternatively, the user may select the notification/data button9010 d to receive the notification of the activation.

When the drug delivery device 9010 and the mobile device 9011 are linkedvia the short range wireless communication based on the deviceactivation, the mobile device 9011 may provide notification and guidancerelated to the operation of the drug delivery device 9010. In oneexample, the mobile device 9011 may provide instruction to place thedrug delivery device 9010 on the body of the user.

It is noted that, during the device activation step, the drug deliverydevice 9010 may be in the non-active power mode (i.e., the power andcontrol system 90800 may be receiving power from the power source andthe drive control system 90820 (i.e., motor 90101) may not be receivingpower from the power source).

At step 90903, after the drug delivery device 9010 has been activated,the control unit 90810 may determine the status of the on-body skinsensor 90840. For example, the control unit 90810 may monitor signalsfrom the on-body skin sensor 90840 and/or the electro-mechanical skinsensor to determine whether the drug delivery device 9010 is in contactwith the user's skin or body. When the control unit 90810 determinesthat the on-body skin sensor 90840 is in contact with the skin of theuser for a predetermined amount of time (e.g., 2 minutes), the controlunit 90810 may set a flag to “on”.

It will be appreciated that, the status check of the on-body sensorprovides safety measure for the drug delivery device 9010. Specifically,because the control unit 90810 monitors the on-body sensor indicationsignal for substantial amount of time prior to setting the flag to “on”,any quick contact (for a few seconds) or touch (e.g., by mistake)between the drug delivery device 9010 and the skin of the user may bedisregarded by the control unit 90810. Moreover, any subsequentactivation button press by the user for various operations of the drugdelivery device 9010 may only be recognized by the control unit, upondetermining that the on-body sensor 90840 is on.

At step 90904, the drug delivery device 9010 may provide notification toterminate the drug delivery process if the control unit 90810 determinesthat the drug delivery device 9010 is not in contact with the body ofthe user for the predetermined amount of time. Additionally oralternatively, the drug delivery device 9010 may notify the user of thetermination of the drug delivery process or to properly position thedrug delivery device 9010 via the mobile app 9010 a.

At step 905, the drug delivery device 9010 provides a requestnotification to the user to activate the needle insertion. For example,as described above the request notification may be provided via audibletones (continuous or variable tones) and/or via LED lights of the drugdelivery device 9010 to press the activation button a predeterminednumber of times (e.g., two times) to activate the needle insertion.

In another example, the request notification may be provided via themobile device 9011 after control unit 90810 determines that the “on”status of the on-body skin sensor 90840. In that example, the drugdelivery device mobile app 9010 a may cause the mobile device 9011 toprovide the request notification for activation of the needle insertion.In one example, the mobile device may provide the user with a requestnotification to press the activation button (e.g., two times) toactivate the needle insertion. For example, the request and/ornotification may be provided via a text message. In another example, theuser may receive an indication of the notification of the requestmessage via the notification button 9010 d. Upon selecting the button9010 d, the user may be provided with the request notification message.

At step 90907, the control unit 90810 may determine whether the user hasprovided the appropriate input for the activation of the needleinsertion (e.g., double press of the activation button).

At step 90908, when the control unit 90810 determines that the needleactivation has not been activated within a predetermined amount of time,the method may notify the user to terminate the drug delivery process.In such an example, the control unit 90810 may wait for thepredetermined amount of time, prior to providing the terminationnotification.

At step 90907, the control unit may determine that the user hasresponded to the request notification by executing the needle insertionactivation (e.g., by pressing the activation button according to therequest message). The method then proceeds to step 90909. Alternatively,the user may directly activate the NIM. (i.e., the pump device may beconfigured such that the NIM is mechanically activated by input by theuser).

It is noted that, the user initiated needle insertion activation isbeneficial, as this makes the user aware of the activation of the needleinsertion into the body of the user and/or initiation of the drugdelivery process.

At step 90909, the power and control system 90800, may prepare or primethe drug delivery device 9010. In one example, the power and controlsystem 90800 may activate the needle insertion mechanism 90200, uponreceiving user activation at step 90907.

Additionally, the power and control system may prime or initiate theSFPC sub-system 90300. It is contemplated that, in some embodiments, theSFPC may be initiated when the drug is being delivered (e.g., at step90921), or concurrently with the needle insertion activation. In oneexample, during the priming of the device, the piston may be controlledto fill the fluid conduit with fluid drug, thereby displacing any airoriginally present therein.

It is noted that, during the steps 90901, 90903, 90904, 90907 and 90908the power and control system may be in non-active power mode (i.e., thedrive control system 90820 or motor 90101 may not be receiving any powerfrom the power source). Whereas, during the needle insertion activationand/or SFPC, for example, the drug delivery device 9010 may be in activepower mode.

At step 90911, timer unit 90812 may be initiated automatically. Forexample, the control unit 90810 may initialize the timer unit 90812which may start the wait time period. Optionally, the wait time periodmay be monitored by the mobile device 9011. For example, upon theinitiation of the timer unit 90812, the control unit 90810 maycommunicate the timing information (e.g., when the timer was initiated,the amount of time left before the drug delivery, etc.) to the mobiledevice 9011. The user may receive such timing information via app 9011 a(e.g., by pressing timer button 9010 c).

It is noted that, the control unit 90810 may access or consult the timerunit 90812 to monitor a wait time period or a delay period. The waittime period may correspond to a time period that needs to be elapsedprior to the initiation of the drug delivery. In one example, the waittime period may be pre-programmed in the power and control system 90800.In one example, the wait time period may be 27 hours. Alternatively, thewait time period may be any other suitable time period for the drugdelivery process.

Moreover, during the wait time period, the drug delivery device 9010 maybe in the non-active power mode. In one example, the drug deliverydevice 9010 may communicate with the mobile device 9011 intermittentlyduring the wait time period. For example, the control unit 90810 via thecommunication unit 90830 of the drug delivery device 9010 may send astatus signal (e.g., a ping signal) to the mobile device 9011 toindicate that the drug delivery device 9010 is operational.Additionally, the drug delivery device 9010 may send information relatedto timing information (as discussed above) to the mobile device 9011.

At step 90913, the power and control system 90800 may monitor sensorsignals from the various internal and/or external sensors. For example,the control unit 90810 may monitor signals from the temperature sensor90880 to determine the temperature of the drug. In one example, thecontrol unit 90810 may process the detected temperature values todetermine that the drug has reached predetermined optimal temperaturefor drug delivery. The drug delivery device 9010 may send thetemperature information of the drug to the mobile device 9011, duringthe wait time period. The mobile device 9011 may process such receiveddata to provide further notification to the user during the wait timeperiod. Step 90913 may also include the continuous monitoring of theon-body sensor by the control unit. In the event that the on-body sensorindicates to the control system 90800 that the pump device 9010 is notin contact with the patient's skin, the control system may provide anotification to the user.

Optionally, the control unit 90810 may request the mobile device 9011 tomonitor signals or data from external sensors such as the glucose ratemonitor 9011 b and the heart rate monitor 9011 a, and further processthe captured data.

In one example, based on the request signal from the drug deliverydevice 9010, the mobile app 9010 a may process the data received fromthe external sensors to determine various operations of the drugdelivery process. For example, based on the data received from theexternal sensors, the mobile app 9010 a may determine an adjusted drugdelivery rate of the drug that may be delivered to the patient.

In one example, a user may work-out during the wait time period, duringwhich, the mobile app 9010 a may monitor the heart rate of the user bycommunicating with the heart rate monitor 9011 a. The mobile app 9010 amay execute an algorithm to determine and adjust the drug delivery ratebased on the change in the heart rate of the user. Additionally, oralternatively, the mobile app 9010 a may communicate with the glucoserate monitor 9011 b to determine and adjust the drug delivery rate basedon the change in the glucose rate of the user. Accordingly, the mobileapp 9011 a may provide notification and instruction that providesinformation as to how to deliver the drug at the adjusted rate. In oneexample, the user may access such information via the notificationbutton 9010 d. For example, the notification may include the number oftimes the user needs to press the activation button on the drug deliverydevice 9010 to deliver the drug at the adjusted rate. During the drugdelivery period, the control unit 90810 of drug delivery device 9010,upon receiving such specified activation signal (e.g., the number of thepress of activation button), may consult the storage unit 90813 totranslate the adjusted delivery rate information into the drivemechanism information (e.g., gear ratio of various gear assemblies, rateof rotation of the motor 90101, etc.) in order to deliver the drug atthe adjusted delivery rate. For example, the control unit 90810 maycontrol the regulating mechanism 90500 or the flow-rate controlsub-system 90825 via the drive control system 90820.

Optionally, in another example, the mobile device 9011 may wirelesslycommunicate the adjusted drug delivery rate to the drug delivery device9010, and the drug delivery device 9010 may automatically deliver thedrug at the adjusted rate when the predetermined wait time periodexpires. In that example, the user may not need to press the activationbutton to adjust the delivery rate of the drug.

Yet in another example, for a bolus delivery of the drug, the drugdelivery device 9010 may not adjust the delivery rate. In that example,the control unit 90810 may monitor the temperature of the drug duringthe wait time period, and deliver the drug to the user after the waittime period elapses. Optionally, after the wait time period has elapsed,drug delivery may be further delayed if the temperature of the drugand/or drug container is below a predefined value. Additionally, themobile app 9011 a may provide notification to the user prior to thedelivery of the drug.

At step 90915, the drug delivery device 9010 may determine whether thewait time period has elapsed and/or nearing the end of the wait timeperiod. For example, the control unit 810, upon consulting the timerunit 90812, may perform the determination.

In one example, the control unit 90810 may determine that the wait timeperiod has elapsed and/or nearing the end of the wait time period. Themethod may then proceed to step 90917.

However, if it is determined that the wait time period has not elapsedand/or not near the wait time period (e.g., if the control unit 90810performs the check 4 hours prior to the end of the wait time period),the method goes back to step 90913.

In one example, for a bolus delivery process, at step 90917, the drugdelivery device 9010 provides notification to the user to indicate thatthe wait time period has elapsed and/or the end of the wait time periodis approaching. The notification may further indicate that the drugdelivery will be initiated. For example, as described above, thenotification may be provided via audible tones (continuous or variabletones) and/or via LED lights of the drug delivery device 9010. Inanother example, the notification may be provided via the mobile device9011. As described above, the mobile device 9010 may receive indicationsignal from the drug delivery device 9010, or alternatively, maydetermine that the drug is to be delivered. Accordingly, the mobiledevice 9011 may then provide the appropriate notification to the user.

In another example, the drug device may be configured such that the userhas the option of initiating drug delivery near to the completion of thewait time, or soon thereafter. In such a scenario, the notification maybe provided just before the predetermined time has elapsed (e.g., about5 minutes before the 27 hour wait period). This may provide the userwith sufficient time to prepare and initiate the drug delivery process.For example, the user may be in an office meeting when the predeterminedwait time period is about to elapse, and may not be aware of the waittime period. As such, if the user receives the alarm or notificationalert prior to end of the wait time period, the user may have sufficienttime to step out of the office meeting to initiate the drug delivery, orsimply initiate the drug delivery while at the meeting.

In another example, the notification may be provided via the pump device9010 or mobile device 9011 after or near the wait time periodexpiration. In that example, the drug delivery device mobile app 9010 amay cause the mobile device 9011 to provide notification, as describedabove. In one example, the mobile app 9010 a may further provide theuser with a request message to prepare to initiate the drug delivery(based on the monitored external sensor data). For example, the requestand/or notification may be provided via a text message. In anotherexample, the user may receive an indication of the notification of therequest message via the notification button 9010 d. Upon selecting thebutton 9010 d, the user may be provided with the request and/or thenotification message. Alternatively, or in addition, the pump device mayprovide notification to the user of the expiration of the wait timeperiod through audible tones, visual indications, or other means.

It is contemplated that, the mobile drug delivery device app 9010 a maytrack the wait time period. For example, the user may select the timerbutton 9010 c to gather information such as how much time is left or howmuch time has elapsed in the wait time period prior to the drugdelivery. In some examples, based on the information, the user mayterminate the drug delivery process, or send information to the drugdelivery device 9010.

As described above, the notification may further provide instructionrelated to the delivery of adjusted drug delivery rate to the user. Thepower and control system 800 may determine if the user has activated theinitiation of the drug delivery within a predetermined time. Forexample, the control unit 90810 may determine whether the activationbutton has been pressed (e.g., within about 2 minutes), after thenotification.

If the drug delivery device 9010 determines that the user has notprovided any input to initiate the drug delivery process within thepredetermined time at the adjusted rate, the control unit 90810 mayterminate the drug delivery process. However, if the user provides theinput for activation within the predetermined time upon receiving thenotification, the method then proceeds to step 90919.

Optionally, as shown in FIG. 9B, the pump device 9010 may be configuredsuch that, the user has the option to initiate drug delivery within somepredetermined time after completion of the wait time period. If the userdoes not initiate drug delivery within this predetermined time, the pumpdevice may automatically initiate drug delivery at the expiration of thepredetermined time.

At step 90919, the power and control system 90800 may provideinstructions to the drive control system 90820 to control the variousdrive mechanisms of the drug delivery device 9010 to deliver the drugafter the predetermined wait time period.

For example, the control unit of the power and control system 90800 maytranslate the delivery rate information to the settings andconfigurations for the various components of the drive control system toenable the delivery of the drug according to the determined deliveryrate. As described above, the translation may include consulting lookuptables and/or databases stored in the storage units. Alternatively, thepower and control system 90810 may send the delivery rate information tothe drive control system 90820, and another controller (not shown) ofthe drive control system may perform the translation to enable thedelivery of the drug according to the determined delivery rate, asdescribed above.

Optionally, at step 90919, the power and control system 90800 mayappropriately change (e.g., increase or decrease) the drug deliveryrate, based on the processed data received from the external sensors(e.g., based on the heart rate and/or the glucose rate information ofthe user, as described at step 90913).

Accordingly, the control unit 90810 may instruct the drive controlsystem 90820 to initiate the drug delivery process (irrespective of theuser activation). The drive control system may then deliver the drug bycontrolling via the drive mechanism 90100.

It is contemplated that, in some examples, the power and control system90800 may instruct the drive control system to initiate the insertionmechanism 90200 and create the connection between the drug container andthe sterile pathway during the drug delivery, after the predeterminedwait time period has elapsed. In such a scenario, the user may providethe input for the NIM activation after the predetermined time haselapsed. In another embodiment, the NIM is activated by the power andcontrol system 90800 prior to initiation of drug delivery.

At step 90921, the power and control system 90810 may determine whetherthe delivery of the drug has ended. For example, motor 90101 may receivesignal from the tether sensor 90875, a valve sensor 90877 and/orpressure sensor 90870 that indicates an end-of-dose of the drug.Accordingly, the drive control system 90820 may then communicate theend-of-dose information to the control unit 90810. The method thenproceeds to step 90923.

When the drug delivery device 9010 determines that the drug has beendelivered, the power and control system 90800 may provide notificationvia audible tones and/or LED lights as described above. Additionallyand/or alternatively, notification of the end-of-dose information may beprovided by the drug delivery device 9010 via the drug delivery devicemobile app 9010 a.

In one example, the drug delivery device 9010 may determine that thedrug has not been delivered or the end-of-dose did not occur in apredetermined amount of time. In such a case, the drug delivery device9010 may provide error notification (e.g., via the LED lights and/or viathe drug delivery device mobile app 9010 a), and the method may then goback to step 90919. Alternatively, the power and control system 90800may terminate drug delivery and/or activate retraction of the NIM if anend-of-dose signal is not received within the expected delivery time.

At step 90923, upon the determination that the end-of-dose of the drughas occurred (i.e., the drug has been delivered in a predetermined timeand/or according to a desired rate of delivery), the drug deliverydevice 9010 may communicate various end-of delivery information to thedrug delivery device mobile app 9010 a. The mobile app 9010 a may thencause the mobile device 9011 to transmit such information to one or moreremote servers or storage 9011 c of various entities (e.g., healthcareprovider, health insurance provider, drug manufacturer, etc.). In oneexample, data stored in the drug delivery device app 9010 a related tothe end of delivery information may be transmitted to the cloud server9011 c via cellular network interface. Moreover, the end of deliveryinformation may include, but is not limited to, validation of theend-of-dose, total time period of the drug delivery, delivery rateinformation, etc. In one example, a user may select the button 9010 d ofthe mobile app 9010 a to transfer such information. In one example, themobile app 9010 a may be configured to selectively transfer the end ofdelivery information to the various entities. It is contemplated that,the end of delivery information, and/or any other information related tothe drug delivery may not be stored permanently upon transfer of suchinformation to the cloud server 9011 c.

FIGS. 77B and 77C show alternative methods of operation of the pumpdevice 9010 and/or mobile device 9011. In the methods illustrated inFIGS. 77B and 9C, activation of the device initiates the timer to markthe beginning of the predetermined wait time. Additionally, deviceactivation also initiates the first step in the NIM activation process.As shown in the figures, the first step in the NIM activation processmay be to determine if the on-body sensor detects the presence of atarget. If the target is detected for the required time period, thedevice may be prepared for NIM activation. The preparation of the devicefor NIM activation may include configuring one or more of the drivemechanism, regulating mechanism, and actuation mechanism such that theuser may activate the NIM. After the device is prepared for NIMactivation, the user may be notified to activate the NIM. Thenotification may be in the form of audible, visual, or tactile feedbackfrom the pump device. Alternatively, or additionally, the notificationmay be provided by the mobile device.

After notification, the user may activate the NIM to insert the fluidpath into the target. For example, the user may activate the NIM bydepressing or actuating the actuation mechanism or another mechanism ofthe pump device.

As shown in FIG. 77B, after the predetermined wait time has elapsed, theuser may be notified that the pump device may be activated to begin drugdelivery. The user may be able to initiate drug delivery within apredetermined “user initiation time.” After the user initiation time haselapsed, the pump device may automatically initiate drug delivery. Theuser may, optionally, be notified upon initiation of drug delivery. Thenotification may in the form of visual, audible, or tactile indicationby the pump device or, alternatively, by notification by the mobiledevice.

In the method shown in FIG. 77C, the pump device 9010 is configured suchthat drug delivery is automatically initiated after the wait timeelapses. The user may be notified that drug delivery will be, or hasbeen, initiated. The user may be notified by an audible, visual, ortactile notification from the pump device. Alternatively, the user maybe notified by the mobile device.

Assembly and/or manufacturing of controlled delivery drive mechanism90100, drug delivery pump 9010, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9050 may first be assembledand filled with a fluid for delivery to the user. The drug container9050 includes a cap 9052, a pierceable seal 9056, a barrel 9058, and aplunger seal 9060. The pierceable seal 9056 may be fixedly engagedbetween the cap 9052 and the barrel 9058, at a distal end of the barrel9058. The barrel 9058 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9060 from theproximal end of the barrel 9058. An optional connection mount 9054 maybe mounted to a distal end of the pierceable seal 9056. The connectionmount 9054 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9058 of the drug container 9050. Thedrug container 9050 may then be mounted to a distal end of drive housing90130.

One or more drive biasing members 90122 may be inserted into a distalend of the drive housing 90130. Optionally, a cover sleeve 90140 may beinserted into a distal end of the drive housing 90130 to substantiallycover biasing member 90122. A piston may be inserted into the distal endof the drive housing 90130 such that it resides at least partiallywithin an axial pass-through of the biasing member 90122 and the biasingmember 90122 is permitted to contact a piston interface surface 90110Cof piston 90110A, 90110B at the distal end of the biasing member 90122.An optional cover sleeve 90140 may be utilized to enclose the biasingmember 90122 and contact the piston interface surface 90110C of piston90110A, 90110B. The piston 90110A, 90110B and drive biasing member90122, and optional cover sleeve 90140, may be compressed into drivehousing 90130. Such assembly positions the drive biasing member 90122 inan initial compressed, energized state and preferably places a pistoninterface surface 90110C in contact with the proximal surface of theplunger seal 9060 within the proximal end of barrel 9058. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 90130 prior to attachment or mounting of the drug container9050. The tether 90525 is pre-connected to the proximal end of thepiston 90110A, 90110B and passed through the axial aperture of thebiasing member 90122 and drive mechanism 90130, and then wound throughthe interior of the drug delivery device with the other end of thetether 90525 wrapped around the winch drum/gear 90520 of the regulatingmechanism 90500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 69B.

Certain optional standard components or variations of drive mechanism90100 or drug delivery device 9010 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9018 to enablethe user to view the operation of the drug delivery device 9010 orverify that drug dose has completed. Similarly, the drug delivery device9010 may contain an adhesive patch 9026 and a patch liner 9028 on thebottom surface of the housing 9012. The adhesive patch 9026 may beutilized to adhere the drug delivery device 9010 to the body of the userfor delivery of the drug dose. As would be readily understood by onehaving ordinary skill in the art, the adhesive patch 9026 may have anadhesive surface for adhesion of the drug delivery device to the body ofthe user. The adhesive surface of the adhesive patch 9026 may initiallybe covered by a non-adhesive patch liner 9028, which is removed from theadhesive patch 9026 prior to placement of the drug delivery device 9010in contact with the body of the user. Removal of the patch liner 9028may further remove the sealing membrane 254 of the insertion mechanism90200, opening the insertion mechanism to the body of the user for drugdelivery (as shown in FIG. 69C).

Similarly, one or more of the components of controlled delivery drivemechanism 90100 and drug delivery device 9010 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9010 is shown as two separate components upper housing9012A and lower housing 9012B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The embodiments described herein providedrive mechanisms for the controlled delivery of drug substances and drugdelivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The controlled deliverydrive mechanisms of the present disclosure may be directly or indirectlyactivated by the user. Furthermore, the configurations of the controlleddelivery drive mechanism and drug delivery devices of the presentdisclosure maintain the sterility of the fluid pathway during storage,transportation, and through operation of the device. Because the paththat the drug fluid travels within the device is entirely maintained ina sterile condition, only these components need be sterilized during themanufacturing process. Such components include the drug container of thedrive mechanism, the fluid pathway connector, the sterile fluid conduit,and the insertion mechanism. In at least one embodiment of the presentdisclosure, the power and control system, the assembly platform, thecontrol arm, the activation mechanism, the housing, and other componentsof the drug delivery device do not need to be sterilized. This greatlyimproves the manufacturability of the device and reduces associatedassembly costs. Accordingly, the devices of the present disclosure donot require terminal sterilization upon completion of assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connector, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a user, wherein aregulating mechanism acting to restrain the distribution of a tether isutilized to meter the free axial translation of the piston. The methodof operation of the drive mechanism and the drug delivery device may bebetter appreciated with reference to FIGS. 70A-70D and FIGS. 71A-71D, asdescribed above.

IX. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B and 33A-33C, may be configured to incorporate the embodiments ofthe drive mechanism described below in connection with FIGS. 69A-75B and78A-79B. The embodiments of the drive mechanism described below inconnection with FIGS. 69A-75B and 78A-79B may be used to replace, in itsentirety or partially, the above-described drive mechanism 100, 6100, or8100, or any other drive mechanism described herein, where appropriate.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances, controlled drug delivery pumpswith such drive mechanisms, the methods of operating such devices, andthe methods of assembling such devices. Notably, the multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The novel embodiments of the present disclosurethus are capable of delivering drug substances at variable rates. Thedrive mechanisms of the present disclosure may be pre-configurable ordynamically configurable, such as by control by the power and controlsystem, to meet desired delivery rates or profiles, as explained indetail below. Additionally, the drive mechanisms of the presentdisclosure provide integrated status indication features which providefeedback to the user before, during, and after drug delivery. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. Because theend-of-dose indication is related to the physical end of axialtranslation and/or travel of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the novel devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a multi-functiondrive mechanism which includes an actuator, a gear assembly including amain gear, a drive housing, and a drug container having a cap, apierceable seal (not visible), a barrel, and a plunger seal. The maingear may be, for example, a star gear disposed to contact multiplesecondary gears or gear surfaces. A drug chamber, located within thebarrel between the pierceable seal and the plunger seal, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. A piston, and one or morebiasing members, wherein the one or more biasing members are initiallyretained in an energized state and is configured to bear upon aninterface surface of the piston, may also be incorporated in themulti-function drive mechanism. The piston is configured to translatesubstantially axially within a drug container having a plunger seal anda barrel. A tether is connected at one end to the piston and at anotherend to a winch drum/gear of a regulating mechanism, wherein the tetherrestrains the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The drug container may contain a drugfluid within a drug chamber for delivery to a user. Optionally, a coversleeve may be utilized between the biasing member and the interfacesurface of the piston to hide the interior components of the barrel(namely, the piston and the biasing member) from view during operationof the drive mechanism. The tether is configured to be released from awinch drum/gear of a regulating mechanism of the multi-function drivemechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In at least one embodiment of the present disclosure, the regulatingmechanism is gear assembly driven by an actuator of the multi-functiondrive mechanism. The regulating mechanism retards or restrains thedistribution of tether, only allowing it to advance at a regulated ordesired rate. This restricts movement of piston within barrel, which ispushed by one or more biasing members, hence controlling the movement ofplunger seal and delivery of the drug contained in chamber. As theplunger seal advances in the drug container, the drug substance isdispensed through the sterile pathway connection, conduit, insertionmechanism, and into the body of the user for drug delivery. The actuatormay be a number of power/motion sources including, for example, a motor(e.g., a DC motor, AC motor, or stepper motor) or a solenoid (e.g.,linear solenoid, rotary solenoid). In a particular embodiment, theactuator is a rotational stepper motor with a notch that correspondswith the gear teeth of the main/star gear.

The regulating mechanism may further include one or more gears of a gearassembly. One or more of the gears may be, for example, compound gearshaving a small diameter gear attached at a shared center point to alarge diameter gear. The gear assembly may include a winch gear coupledto a winch drum/gear upon which the tether may be releasably wound.Accordingly, rotation of the gear assembly initiated by the actuator maybe coupled to winch drum/gear (i.e., through the gear assembly), therebycontrolling the distribution of tether, the rate of expansion of thebiasing members and the axial translation of the piston, and the rate ofmovement of plunger seal within barrel to force a fluid from drugchamber. The rotational movement of the winch drum/gear, and thus theaxial translation of the piston and plunger seal, are metered,restrained, or otherwise prevented from free axial translation by othercomponents of the regulating element, as described herein. Notably, theregulating mechanisms of the present disclosure do not drive thedelivery of fluid substances from the drug chamber. The delivery offluid substances from the drug chamber is caused by the expansion of thebiasing member from its initial energized state acting upon the pistonand plunger seal. The regulating mechanisms instead function to provideresistance to the free motion of the piston and plunger seal as they arepushed by the expansion of the biasing member from its initial energizedstate. The regulating mechanism does not drive the delivery but onlycontrols the delivery motion. The tether limits or otherwise restrainsthe motion of the piston and plunger seal, but does not apply the forcefor the delivery.

In addition to controlling the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer (thereby delivering drug substances at variable rates and/ordelivery profiles); the multi-function drive mechanisms of the presentdisclosure may concurrently or sequentially perform the steps of:triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a user; and connecting a sterile fluid pathway to adrug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. In at least oneembodiment, initial motion by the actuator of the multi-function drivemechanism causes rotation of main/star gear. In one manner, main/stargear conveys motion to the regulating mechanism through gear assembly.In another manner, main/star gear conveys motion to the needle insertionmechanism through gear. As gear is rotated by main/star gear, gearengages the needle insertion mechanism to initiate the fluid pathwayconnector into the user, as described in detail above. In one particularembodiment, needle insertion mechanism is a rotational needle insertionmechanism. Accordingly, gear is configured to engage a correspondinggear surface of the needle insertion mechanism. Rotation of gear causesrotation of needle insertion mechanism through the gear interactionbetween gear of the drive mechanism and corresponding gear surface ofthe needle insertion mechanism. Once suitable rotation of the needleinsertion mechanism occurs, the needle insertion mechanism may beinitiated to create the fluid pathway connector into the user, asdescribed in detail herein.

In at least one embodiment, rotation of the needle insertion mechanismin this manner may also cause a connection of a sterile fluid pathway toa drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. Ramp aspect ofneedle insertion mechanism is caused to bear upon a movable connectionhub of the sterile fluid pathway connector. As the needle insertionmechanism is rotated by the multi-function drive mechanism, ramp aspectof needle insertion mechanism bears upon and translates movableconnection hub of the sterile fluid pathway connector to facilitate afluid connection therein. In at least one embodiment, the needleinsertion mechanism may be configured such that a particular degree ofrotation enables the needle/trocar to retract as detailed above.Additionally or alternatively, such needle/trocar retraction may beconfigured to occur upon a user-activity or upon movement or function ofanother component of the drug delivery device. In at least oneembodiment, needle/trocar retraction may be configured to occur uponend-of-drug-delivery, as triggered by, for example, the regulatingmechanism and/or one or more of the status readers as described herein.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug delivery pump having ahousing and an assembly platform, upon which an activation mechanism, aninsertion mechanism, a fluid pathway connector, a power and controlsystem, and a controlled delivery drive mechanism may be mounted, saiddrive mechanism having a drive housing, a piston, and a biasing member,wherein the biasing member is initially retained in an energized stateand is configured to bear upon an interface surface of the piston. Thepiston is configured to translate substantially axially within a drugcontainer having a plunger seal and a barrel. A tether is connected atone end to the piston and at another end to a winch drum/gear of adelivery regulating mechanism, wherein the tether restrains the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The drug container may contain a drug fluid within a drug chamberfor delivery to a user. Optionally, a cover sleeve may be utilizedbetween the biasing member and the interface surface of the piston tohide the interior components of the barrel (namely, the piston and thebiasing member) from view during operation of the drive mechanism. Thetether is configured to be released from a winch drum/gear of thedelivery regulating mechanism to meter the free expansion of the biasingmember from its initial energized state and the free axial translationof the piston upon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum/gear upon which the tether may be releasably wound, rotationof the winch drum/gear releases the tether from the winch drum/gear tometer the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The metering of the tether controls therate or profile of drug delivery to a user. The piston may be one ormore parts and connects to a distal end of the tether. The winchdrum/gear is coupled to a regulating mechanism which controls rotationof the winch drum/gear and hence metering of the translation of thepiston.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch drum/gear and thereby permit axialtranslation of the piston by the biasing member to translate a plungerseal within a barrel. The one or more inputs may be provided by theactuation of the activation mechanism, a control interface, and/or aremote control mechanism. The power and control system may be configuredto receive one or more inputs to adjust the restraint provided by thetether and winch drum/gear on the free axial translation of the pistonupon which the biasing member bears upon to meet a desired drug deliveryrate or profile, to change the dose volume for delivery to the user,and/or to otherwise start, stop, or pause operation of the drivemechanism.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of the actuator. The change in the rate of movement ofthe actuator causes a change in the rotation rate of the regulatingmechanism which, in turn, controls the rate of drug delivery to theuser. Alternatively, the delivery profile may be altered by a change inthe characteristics of the flow path of medicament through the conduitconnecting the drug container and insertion mechanism. The change may becaused by the introduction, removal, or modification of a flowrestrictor which restricts flow of medicament from the drug container tothe insertion mechanism. For example, a flow restrictor may havemultiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

The novel embodiments of the present disclosure provide drive mechanismswhich are capable of metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thereby, controlling therate of delivery of drug substances. The novel control delivery drivemechanisms are additionally capable of providing the incremental statusof the drug delivery before, during, and after operation of the device.Throughout this specification, unless otherwise indicated, “comprise,”“comprises,” and “comprising,” or related terms such as “includes” or“consists of,” are used inclusively rather than exclusively, so that astated integer or group of integers may include one or more othernon-stated integers or groups of integers. As will be described furtherbelow, the embodiments of the present disclosure may include one or moreadditional components which may be considered standard components in theindustry of medical devices. For example, the embodiments may includeone or more batteries utilized to power the motor, drive mechanisms, anddrug delivery devices of the present disclosure. The components, and theembodiments containing such components, are within the contemplation ofthe present disclosure and are to be understood as falling within thebreadth and scope of the present disclosure.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances and drug delivery pumps whichincorporate such multi-function drive mechanisms. The multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The drive mechanisms of the present disclosurecontrol the rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container and, thus, are capableof delivering drug substances at variable rates and/or deliveryprofiles. Additionally, the drive mechanisms of the present disclosureprovide integrated status indication features which provide feedback tothe user before, during, and after drug delivery. For example, the usermay be provided an initial feedback to identify that the system isoperational and ready for drug delivery. Upon activation, the system maythen provide one or more drug delivery status indications to the user.At completion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication.

As used herein to describe the drive mechanisms, drug delivery pumps, orany of the relative positions of the components of the presentdisclosure, the terms “axial” or “axially” refer generally to alongitudinal axis “A” around which the drive mechanisms are preferablypositioned, although not necessarily symmetrically there-around. Theterm “radial” refers generally to a direction normal to axis A. Theterms “proximal,” “rear,” “rearward,” “back,” or “backward” refergenerally to an axial direction in the direction “P”. The terms“distal,” “front,” “frontward,” “depressed,” or “forward” refergenerally to an axial direction in the direction “D”. As used herein,the term “glass” should be understood to include other similarlynon-reactive materials suitable for use in a pharmaceutical gradeapplication that would normally require glass, including but not limitedto certain non-reactive polymers such as cyclic olefin copolymers (COC)and cyclic olefin polymers (COP). The term “plastic” may include boththermoplastic and thermosetting polymers. Thermoplastic polymers can bere-softened to their original condition by heat; thermosetting polymerscannot. As used herein, the term “plastic” refers primarily to moldablethermoplastic polymers such as, for example, polyethylene andpolypropylene, or an acrylic resin, that also typically contain otheringredients such as curatives, fillers, reinforcing agents, colorants,and/or plasticizers, etc., and that can be formed or molded under heatand pressure. As used herein, the term “plastic” is not meant to includeglass, non-reactive polymers, or elastomers that are approved for use inapplications where they are in direct contact with therapeutic liquidsthat can interact with plastic or that can be degraded by substituentsthat could otherwise enter the liquid from plastic. The term“elastomer,” “elastomeric” or “elastomeric material” refers primarily tocross-linked thermosetting rubbery polymers that are more easilydeformable than plastics but that are approved for use withpharmaceutical grade fluids and are not readily susceptible to leachingor gas migration under ambient temperature and pressure. “Fluid” refersprimarily to liquids, but can also include suspensions of solidsdispersed in liquids, and gasses dissolved in or otherwise presenttogether within liquids inside the fluid-containing portions of the drugdelivery devices. According to various aspects and embodiments describedherein, reference is made to a “biasing member”, such as in the contextof one or more biasing members for asserting force on a plunger seal. Itwill be appreciated that the biasing member may be any member that iscapable of storing and releasing energy. Non-limiting examples include aspring, such as for example a coiled spring, a compression or extensionspring, a torsional spring, or a leaf spring, a resiliently compressibleor elastic band, or any other member with similar functions. In at leastone embodiment of the present disclosure, the biasing member is aspring, preferably a compression spring.

The novel devices of the present disclosure provide drive mechanismswith integrated status indication and drug delivery pumps whichincorporate such drive mechanisms. Such devices are safe and easy touse, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. The novel devices of the presentdisclosure provide these desirable features without any of the problemsassociated with known prior art devices. Certain non-limitingembodiments of the novel drug delivery pumps, drive mechanisms, andtheir respective components are described further herein with referenceto the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.69A-69C show an exemplary drug delivery device according to at least oneembodiment of the present disclosure with the top housing removed sothat the internal components are visible. The drug delivery device maybe utilized to administer delivery of a drug treatment into a body of auser. As shown in FIGS. 69A-69C, the drug delivery device 9010 includesa pump housing 9012. Pump housing 9012 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug delivery device. Forexample, drug delivery device 9010 includes a pump housing 9012 whichmay include an upper housing and a lower housing (not shown for ease ofviewing internal components). The pump housing 9012 may include one ormore tamper evidence features to identify if the drug delivery devicehas been opened or tampered with. For example, the pump housing 9012 mayinclude one or more tamper evidence labels or stickers, such as labelsthat bridge across the upper housing and the lower housing. Additionallyor alternatively, the housing 9012 may include one or more snap arms orprongs connecting between the upper housing and the lower housing. Abroken or altered tamper evidence feature would signal to the user, thephysician, the supplier, the manufacturer, or the like, that the drugdelivery device has potentially been tampered, e.g., by accessing theinternal aspects of the device, so that the device is evaluated andpossibly discarded without use by or risk to the user. The drug deliverydevice may further include an activation mechanism, a status indicator,and a window. Window may be any translucent or transmissive surfacethrough which the operation of the drug delivery device may be viewed.As shown in FIG. 69B, drug delivery device 9010 further includesassembly platform 9020, sterile fluid conduit 30, drive mechanism 90100having drug container 9050, insertion mechanism 90200, fluid pathwayconnector 90300, and a power and control system (not shown). One or moreof the components of such drug delivery devices may be modular in thatthey may be, for example, pre-assembled as separate components andconfigured into position onto the assembly platform 9020 of the drugdelivery device 9010 during manufacturing.

The pump housing 9012 contains all of the device components and providesa means of removably attaching the device 9010 to the skin of the user.The pump housing 9012 also provides protection to the interiorcomponents of the device 9010 against environmental influences. The pumphousing 9012 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9012 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9012 may include certaincomponents, such as one or more status indicators and windows, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9010 provides anactivation mechanism that is displaced by the user to trigger the startcommand to the power and control system. In a preferred embodiment, theactivation mechanism is a start button that is located through the pumphousing 9012, such as through an aperture between upper housing andlower housing, and which contacts either directly or indirectly thepower and control system. In at least one embodiment, the start buttonmay be a push button, and in other embodiments, may be an on/off switch,a toggle, or any similar activation feature known in the art. The pumphousing 9012 also provides one or more status indicators and windows. Inother embodiments, one or more of the activation mechanism, the statusindicator, the window, and combinations thereof may be provided on theupper housing or the lower housing such as, for example, on a sidevisible to the user when the drug delivery device 9010 is placed on thebody of the user. Housing 9012 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device 9010 is configured such that, upon activation by auser by depression of the activation mechanism, the multi-function drivemechanism is activated to: insert a fluid pathway into the user; enable,connect, or open necessary connections between a drug container, a fluidpathway, and a sterile fluid conduit; and force drug fluid stored in thedrug container through the fluid pathway and fluid conduit for deliveryinto a user. In at least one embodiment, such delivery of drug fluidinto a user is performed by the multi-function drive mechanism in acontrolled manner. One or more optional safety mechanisms may beutilized, for example, to prevent premature activation of the drugdelivery device. For example, an optional on-body sensor (not visible)may be provided in one embodiment as a safety feature to ensure that thepower and control system, or the activation mechanism, cannot be engagedunless the drug delivery device 9010 is in contact with the body of theuser. In one such embodiment, the on-body sensor is located on thebottom of lower housing where it may come in contact with the user'sbody. Upon displacement of the on-body sensor, depression of theactivation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor is a mechanical safety mechanism, such asfor example a mechanical lock out, that prevents triggering of the drugdelivery device 9010 by the activation mechanism. In another embodiment,the on-body sensor may be an electro-mechanical sensor such as amechanical lock out that sends a signal to the power and control systemto permit activation. In still other embodiments, the on-body sensor canbe electrically based such as, for example, a capacitive- orimpedance-based sensor which must detect tissue before permittingactivation of the power and control system. These concepts are notmutually exclusive and one or more combinations may be utilized withinthe breadth of the present disclosure to prevent, for example, prematureactivation of the drug delivery device. In a preferred embodiment, thedrug delivery device 9010 utilizes one or more mechanical on-bodysensors. Additional integrated safety mechanisms are described hereinwith reference to other components of the novel drug delivery devices.

IX.A. Power and Control System

The power and control system may include a power source, which providesthe energy for various electrical components within the drug deliverydevice, one or more feedback mechanisms, a microcontroller, a circuitboard, one or more conductive pads, and one or more interconnects. Othercomponents commonly used in such electrical systems may also beincluded, as would be appreciated by one having ordinary skill in theart. The one or more feedback mechanisms may include, for example,audible alarms such as piezo alarms and/or light indicators such aslight emitting diodes (LEDs). The microcontroller may be, for example, amicroprocessor. The power and control system controls several deviceinteractions with the user and interfaces with the drive mechanism90100. In one embodiment, the power and control system interfaces eitherdirectly or indirectly with the on-body sensor 9024 to identify when thedevice is in contact with the user and/or the activation mechanism toidentify when the device has been activated. The power and controlsystem may also interface with the status indicator of the pump housing9012, which may be a transmissive or translucent material which permitslight transfer, to provide visual feedback to the user. The power andcontrol system interfaces with the drive mechanism 90100 through one ormore interconnects to relay status indication, such as activation, drugdelivery, and end-of-dose, to the user. Such status indication may bepresented to the user via auditory tones, such as through the audiblealarms, and/or via visual indicators, such as through the LEDs. In apreferred embodiment, the control interfaces between the power andcontrol system and the other components of the drug delivery device arenot engaged or connected until activation by the user. This is adesirable safety feature that prevents accidental operation of the drugdelivery device and may additionally maintain the energy contained inthe power source during storage, transportation, and the like.

The power and control system may be configured to provide a number ofdifferent status indicators to the user. For example, the power andcontrol system may be configured such that after the on-body sensorand/or trigger mechanism have been pressed, the power and control systemprovides a ready-to-start status signal via the status indicator ifdevice start-up checks provide no errors. After providing theready-to-start status signal and, in an embodiment with the optionalon-body sensor, if the on-body sensor remains in contact with the bodyof the user, the power and control system will power the drive mechanism90100 to begin delivery of the drug treatment through the fluid pathwayconnector 90300 and sterile fluid conduit 9030 (not shown).

Additionally, the power and control system may be configured to identifyremoval of the drug delivery device from its packaging. The power andcontrol system may be mechanically, electronically, orelectro-mechanically connected to the packaging such that removal of thedrug delivery device from the packaging may activate or power-on thepower and control system for use, or simply enable the power and controlsystem to be powered-on by the user. In such an embodiment, withoutremoval of the drug delivery device from the packaging the drug deliverydevice cannot be activated. This provides an additional safety mechanismof the drug delivery device and for the user. In at least oneembodiment, the drug delivery device or the power and control system maybe electronically or electro-mechanically connected to the packaging,for example, such as by one or more interacting sensors from a range of:Hall effect sensors; giant magneto resistance (GMR) or magnetic fieldsensors; optical sensors; capacitive or capacitance change sensors;ultrasonic sensors; and linear travel, LVDT, linear resistive, orradiometric linear resistive sensors; and combinations thereof, whichare capable of coordinating to transmit a signal between components toidentify the location there-between. Additionally or alternatively, thedrug delivery device or the power and control system may be mechanicallyconnected to the packaging, such as by a pin and slot relationship whichactivates the system when the pin is removed (i.e., once the drugdelivery device is removed from the packaging).

In a preferred embodiment of the present disclosure, once the power andcontrol system has been activated, the multi-function drive mechanism isinitiated to actuate the insertion mechanism 90200 and the fluid pathwayconnector 90300, while also permitting the drug fluid to be forced fromthe drug container. During the drug delivery process, the power andcontrol system is configured to provide a dispensing status signal viathe status indicator. After the drug has been administered into the bodyof the user and after the end of any additional dwell time, to ensurethat substantially the entire dose has been delivered to the user, thepower and control system may provide an okay-to-remove status signal viathe status indicator. This may be independently verified by the user byviewing the drive mechanism and drug dose delivery through the window ofthe pump housing 9012. Additionally, the power and control system may beconfigured to provide one or more alert signals via the statusindicator, such as for example alerts indicative of fault or operationfailure situations.

The power and control system may additionally be configured to acceptvarious inputs from the user to dynamically control the drive mechanisms90100 to meet a desired drug delivery rate or profile. For example, thepower and control system may receive inputs, such as from partial orfull activation, depression, and/or release of the activation mechanism,to set, initiate, stop, or otherwise adjust the control of the drivemechanism 90100 via the power and control system to meet the desireddrug delivery rate or profile. Similarly, the power and control systemmay be configured to receive such inputs to adjust the drug dose volume;to prime the drive mechanism, fluid pathway connector, and fluidconduit; and/or to start, stop, or pause operation of the drivemechanism 90100. Such inputs may be received by the user directly actingon the drug delivery device 9010, such as by use of the activationmechanism 9014 or a different control interface, or the power andcontrol system may be configured to receive such inputs from a remotecontrol device. Additionally or alternatively, such inputs may bepre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism of the drugdelivery device 9010 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

IX.B. Insertion Mechanism

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure, including a rigid needle insertion mechanismand/or a rotational needle insertion mechanism as developed by theassignee of the present disclosure.

In at least one embodiment, the insertion mechanism 90200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 69B and FIG. 69C). The connection of the base to theassembly platform 9020 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9010. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9030 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9027 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane (not visible).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. Displacement of the lockoutpin(s), by one or more methods such as pulling, pushing, sliding, and/orrotation, permits insertion biasing member to decompress from itsinitial compressed, energized state. This decompression of the insertionbiasing member drives the needle and, optionally, the cannula into thebody of the user. At the end of the insertion stage or at the end ofdrug delivery (as triggered by the multi-function drive mechanism), theretraction biasing member is permitted to expand in the proximaldirection from its initial energized state. This axial expansion in theproximal direction of the retraction biasing member retracts the needle.If an inserter needle/trocar and cannula configuration are utilized,retraction of the needle may occur while maintaining the cannula influid communication with the body of the user. Accordingly, theinsertion mechanism may be used to insert a needle and cannula into theuser and, subsequently, retract the needle while retaining the cannulain position for drug delivery to the body of the user.

In at least one embodiment, as shown in FIG. 75, the insertion mechanismincludes a rotationally biased member 90210 which is initially held inan energized state. In a preferred embodiment, the rotationally biasedmember is a torsional spring. The rotational biasing member may beprevented from de-energizing by interaction of gear surface 90208 withgear 90112 or, alternatively, by contact of a component of the insertionmechanism with a rotation prevention feature of the drug deliverydevice. Upon activation of the device, or another input, therotationally biased member 90210 is permitted to, at least partially,de-energize. This causes one or more components of the insertionmechanism to rotate and, in turn, cause, or allow, the insertion of theneedle into the patient. Further, a cannula may be inserted into thepatient as described above. At a later time, such as when the controlarm or another component of the device recognizes a slack in the tether,the rotationally biased member may be allowed to further de-energize,causing additional rotation of one or more components of the insertionmechanism. This rotation may cause, or allow, the needle to be retractedfrom the patient. The needle may be fully retracted in a single step orthere may be multiple steps of retraction.

IX.C. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9010, the fluid pathway connector 90300 isenabled to connect the sterile fluid conduit 9030 to the drug containerof the drive mechanism 90100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 90100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user. In one such embodiment, the fluid pathway connector may besubstantially similar to that described in International PatentApplication No. PCT/US2012/054861, which is included by reference hereinin its entirety for all purposes. In such an embodiment, a compressiblesterile sleeve may be fixedly attached between the cap of the drugcontainer and the connection hub of the fluid pathway connector. Thepiercing member may reside within the sterile sleeve until a connectionbetween the fluid connection pathway and the drug container is desired.The sterile sleeve may be sterilized to ensure the sterility of thepiercing member and the fluid pathway prior to activation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Applications No.PCT/US2013/030478 or No. PCT/US2014/052329, for example, which areincluded by reference herein in their entirety for all purposes.According to such an embodiment, a drug container may have a drugchamber within a barrel between a pierceable seal and a plunger seal. Adrug fluid is contained in the drug chamber. Upon activation of thedevice by the user, a drive mechanism asserts a force on a plunger sealcontained in the drug container. As the plunger seal asserts a force onthe drug fluid and any air/gas gap or bubble, a combination of pneumaticand hydraulic pressure builds by compression of the air/gas and drugfluid and the force is relayed to the sliding pierceable seal. Thepierceable seal is caused to slide towards the cap, causing it to bepierced by the piercing member retained within the integrated sterilefluid pathway connector. Accordingly, the integrated sterile fluidpathway connector is connected (i.e., the fluid pathway is opened) bythe combination pneumatic/hydraulic force of the air/gas and drug fluidwithin the drug chamber created by activation of a drive mechanism. Oncethe integrated sterile fluid pathway connector is connected or opened,drug fluid is permitted to flow from the drug container, through theintegrated sterile fluid pathway connector, sterile fluid conduit, andinsertion mechanism, and into the body of the user for drug delivery. Inat least one embodiment, the fluid flows through only a manifold and acannula and/or needle of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery.

In a preferred embodiment, the sterile fluid pathway connector isinitiated by movement of the needle insertion mechanism, which itself isinitiated by the multi-function drive mechanism. Additionally oralternatively, the sterile fluid pathway connector is initiated bymovement directly of the multi-function drive mechanism. For example,the multi-function drive mechanism may include a rotational gear, suchas the star gear described in detail herein, that acts concurrently orsequentially to control the rate of drug delivery, to actuate the needleinsertion mechanism, and/or initiate the sterile fluid pathwayconnector. In one particular embodiment, shown in FIGS. 69A-69C, themulti-function drive mechanism performs all of these steps substantiallyconcurrently. The multi-function drive mechanism rotates a gear thatacts upon several other components. The gear acts on a gear assembly tocontrol the rate of drug delivery, while also contacting a needleinsertion mechanism to introduce a fluid pathway into the user. As theneedle insertion mechanism is initiated, the sterile fluid connection ismade to permit drug fluid flow from the drug container, through thefluid conduit, into the needle insertion mechanism, for delivery intothe patient as the gear and gear assembly of the multi-function drivemechanism control the rate of drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 90300 and the sterile fluid conduit 9030 are providedhereinafter in later sections in reference to other embodiments.

IX.D. Multi-Function Drive Mechanism:

The multi-function drive mechanisms of the present disclosure enable orinitiate several functions, including: (i) controlling the rate of drugdelivery by metering, providing resistance, or otherwise preventing freeaxial translation of the plunger seal utilized to force a drug substanceout of a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. With reference to the embodiments shown in FIGS.70A-70D and 3A-3D, multi-function drive mechanism 90100 includes anactuator 90101, a gear assembly 90110 including a main gear 90102, adrive housing 90130, and a drug container 9050 having a cap 9052, apierceable seal (not visible), a barrel 9058, and a plunger seal 9060.The main gear 90102 may be, for example, a star gear disposed to contactmultiple secondary gears or gear surfaces. A drug chamber 9021, locatedwithin the barrel 9058 between the pierceable seal and the plunger seal9060, may contain a drug fluid for delivery through the insertionmechanism and drug delivery device into the body of the user. The sealsdescribed herein may be comprised of a number of materials but are, in apreferred embodiment, comprised of one or more elastomers or rubbers.The drive mechanism 90100 may further contain one or more drive biasingmembers, one or more release mechanisms, and one or more guides, as aredescribed further herein. The components of the drive mechanism functionto force a fluid from the drug container out through the pierceableseal, or preferably through the piercing member of the fluid pathwayconnector, for delivery through the fluid pathway connector, sterilefluid conduit, and insertion mechanism into the body of the user.

In one particular embodiment, the drive mechanism 90100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. The fluid pathway connector may beconnected through the pierceable seal prior to, concurrently with, orafter activation of the drive mechanism to permit fluid flow from thedrug container, through the fluid pathway connector, sterile fluidconduit, and insertion mechanism, and into the body of the user for drugdelivery. In at least one embodiment, the fluid flows through only amanifold and a cannula of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detail herein.

Referring now to the embodiment of the multi-function drive mechanismshown in FIGS. 70A-70D and 71A-71D, multi-function drive mechanism 100includes an actuator 90101, a gear assembly 90110 including a main gear90102, a drive housing 90130, and a drug container 9050 having a cap9052, a pierceable seal (not visible), a barrel 9058, and a plunger seal9060. The main gear 90102 may be, for example, a star gear disposed tocontact multiple secondary gears or gear surfaces. A drug chamber 9021,located within the barrel 9058 between the pierceable seal and theplunger seal 9060, may contain a drug fluid for delivery through theinsertion mechanism and drug delivery device into the body of the user.Compressed within the drive housing 90130, between the drug container9050 and the proximal end of the housing 90130, are one or more drivebiasing members 90122 and a piston 90110, wherein the drive biasingmembers 90122 are configured to bear upon an interface surface 90110C ofthe piston 90110, as described further herein. Optionally, a coversleeve (not shown) may be utilized between the drive biasing members90122 and the interface surface 90110C of the piston 90110 to, forexample, promote more even distribution of force from the drive biasingmember 90122 to the piston 90110, prevent buckling of the drive biasingmembers 90122, and/or hide biasing members 90122 from user view.Interface surface 90110C of piston 90110 is caused to rest substantiallyadjacent to, or in contact with, a proximal end of seal 9060. Althoughthe embodiments shown in FIGS. 70A-70D and 71A-71D show a singularbiasing member it is also contemplated that one or more biasing membersdisposed to act in parallel may be used.

As best shown in FIG. 70D and FIG. 71D, the piston 90110 may becomprised of two components 90110A and 90110B and have an interfacesurface 90110C to contact the plunger seal. A tether, ribbon, string, orother retention strap (referred to herein as the “tether” 90525) may beconnected at one end to the piston 90110A, 90110B. For example, thetether 90525 may be connected to the piston 90110A, 90110B by retentionbetween the two components of the piston 90110A, 90110B when assembled.The tether 90525 is connected at another end to a winch drum/gear 90520of a delivery control mechanism 90500. Through the use of the winchdrum/gear 90520 connected to one end of the tether 90525, and the tether90525 connected at another end to the piston 90110A, 90110B, theregulating mechanism 90500 functions to control, meter, provideresistance, or otherwise prevent free axial translation of the piston90110A, 90110B and plunger seal 9060 utilized to force a drug substanceout of a drug container 9050. Accordingly, the regulating mechanism90500 is a portion of the gear assembly 90116 aspect of themulti-function drive mechanism, which together function to control therate or profile of drug delivery to the user.

As shown in FIGS. 70A-70D and 71A-71D, and in isolation in FIGS. 72 and73A-73B, in the embodiments of the present disclosure, the regulatingmechanism 90500 is gear assembly driven by an actuator 90101 of themulti-function drive mechanism 90100. The regulating mechanism retardsor restrains the distribution of tether 90525, only allowing it toadvance at a regulated or desired rate. This restricts movement ofpiston 90110 within barrel 9058, which is pushed by one or more biasingmembers 90122, hence controlling the movement of plunger seal 9060 anddelivery of the drug contained in chamber 9021. As the plunger seal 9060advances in the drug container 9050, the drug substance is dispensedthrough the sterile fluid pathway connector 90300, conduit 9030,insertion mechanism 90200, and into the body of the user for drugdelivery. The actuator 90101 may be a number of power/motion sourcesincluding, for example, a solenoid, a stepper motor, or a rotationaldrive motor. In a particular embodiment, the actuator 90101 is arotational stepper motor with a notch that corresponds with the gearteeth of the main/star gear 90102. Commonly, such a rotational steppermotor may be referred to as a ‘Pac-Man’ motor. In at least oneembodiment, the Pac-Man motor has a gear interface within which one ormore teeth of the main gear may partially reside during operation of thesystem. This is more clearly visible in FIGS. 73A-73B. When the gearinterface 90101A of the Pac-Man motor 90101 is in alignment with a tooth90102A of the main gear 90102, rotational motion of the Pac-Man motor90101 causes gear interface rotation of the main gear 90102. When thePac-Man motor 90101 is between gear teeth of the main gear, it may actas a resistance for, for example, back-spinning or unwinding of the gearassembly 90116. In one particular embodiment, the Pac-Man motor 90101utilizes an alternating direction type motor to rotate the Pac-Man motor90101 backwards and forwards. This configuration aids in the preventionof a runaway condition, where the motor and the gears are freelypermitted to rotate, by using the multi-direction of the motor toprevent continuous spin in one direction (as would be needed for arunaway condition). This bi-directional movement of the motor, coupledwith the use of the gear interface cut within the Pac-Man motor, providesuitable safety features to prevent a runaway condition that couldpotentially lead to over-delivery of drug to the user. Further detailabout the gear assembly 90116, regulating mechanism 90500, andmulti-function drive mechanism 90100 are provided herein.

In a particular embodiment shown in FIGS. 73A-73B, the regulatingelement 90500 further includes one or more gears 90511, 90512, 90513,90514, of a gear assembly 90516. One or more of the gears 90511, 90512,90513, 90514 may be, for example, compound gears having a small diametergear attached at a shared center point to a large diameter gear. Gear90513 may be rotationally coupled to winch drum/gear 90520, for exampleby a keyed shaft, thereby coupling rotation of gear assembly 90516 towinch drum/gear 90520. Compound gear 90512 engages the small diametergear 90513 such that rotational movement of the compound gear aspect90512B is conveyed by engagement of the gears (such as by engagement ofcorresponding gear teeth) to gear 90513. Compound gear aspect 90512A,the rotation of which is coupled to gear aspect 90512B, is caused torotate by action of compound gear aspect 90102B of the main/star gear90102. Compound gear aspect 90102B, the rotation of which is coupled tomain/star gear 90102, is caused to rotate by interaction betweenmain/star gear 90102A and interface 90101A of the actuator 90101. Thus,rotation of main/star gear 90102 is conveyed to winch drum/gear 90520.Accordingly, rotation of the gear assembly 90516 initiated by theactuator 90101 may be coupled to winch drum/gear 90520 (i.e., throughthe gear assembly 90516), thereby controlling the distribution of tether90525, and the rate of movement of plunger seal 9060 within barrel 9058to force a fluid from drug chamber 9021. The rotational movement of thewinch drum/gear 90520, and thus the axial translation of the piston90110 and plunger seal 9060, are metered, restrained, or otherwiseprevented from free axial translation by other components of theregulating element 90500, as described herein. As described above, theactuator 90101 may be a number of known power/motion sources including,for example, a motor (e.g., a DC motor, AC motor, or stepper motor) or asolenoid (e.g., linear solenoid, rotary solenoid).

The embodiment described above and shown in FIGS. 69A-73D show anactuator 90101 that is in vertical alignment and in direct engagementwith the main/star gear 90102. As would readily be appreciated by onehaving ordinary skill in the mechanical arts, the actuator 90101 couldbe modified to be in horizontal alignment. Additionally oralternatively, the actuator 90101 could be modified to be in indirectengagement with the main/star gear 90102. The embodiments shown in FIGS.75A-75B show an actuator 90101 that is in horizontal alignment andindirect engagement with the main/star gear 90102. Such an embodimentmay utilize a rack and pinion engagement, a drive screw, or a worm gear90101W, as shown in FIGS. 75A-75B, to change the direction of motionfrom horizontal to vertical (i.e., perpendicular interaction). Actuator90101 rotates worm gear 90101W, which engages gear 90101G and conveysthe motion to the Pac-Man gear 90101A. The Pac-Man gear 90101A engagesmain/star gear 90102 to enable operation of the drive mechanism and thedrug delivery device, as described herein. Main/star gear 90102 alsodrives operation of gear 90112 to enable operation of the needleinsertion mechanism 90200, as described herein. In one particularembodiment, the actuator 90101 utilizes an alternating direction typemotor to rotate the worm gear 90101W, gear 90101G, and Pac-Man gear90101A backwards and forwards. This configuration aids in the preventionof a runaway condition, where the motor and the gears are freelypermitted to rotate, by using the multi-direction of the motor toprevent continuous spin in one direction (as would be needed for arunaway condition). This bi-directional movement of the actuator 90101,coupled with the use of the gear interface of the worm gear 90101W, gear90101G, and Pac-Man gear 90101A with the main/star gear 90102, providesuitable safety features to prevent a runaway condition that couldpotentially lead to over-delivery of drug to the user. Additionally, theactuator 90101 may include a stop member 90101B that stops the rotationof the Pac-Man gear 90101A against a stop block 90150. Stop block 90150further prevents over-rotation of the Pac-Man gear 90101A and,accordingly, the main/star gear 90102 to prevent a runaway conditionthat could potentially lead to over-delivery of drug to the user. Forthe device to function in this configuration, the Pac-Man gear 90101Amust be rotated backwards the other direction before rotating forwardsagain to progress the main/star gear 90102 because the stop member90101B prevents over rotation in one direction by interaction with thestop block 90150. Additionally, the geometry of worm gear 90101W may beconfigured such that it is self-locking and/or cannot be back-driven bygear 90101G. This may be done by configuration of parameters such as:pitch, lead angle, pressure angle, and number of threads. In so doing,runaway conditions of the drive mechanism will be prevented by the wormgear's resistance to rotations that are not caused by actuator 90101.

Notably, the regulating mechanisms 90500 of the present disclosure donot drive the delivery of fluid substances from the drug chamber 9021.The delivery of fluid substances from the drug chamber 9021 is caused bythe expansion of the biasing member 90122 from its initial energizedstate acting upon the piston 90110A, 90110B and plunger seal 9060. Theregulating mechanisms 90500 instead function to provide resistance tothe free motion of the piston 90110A, 90110B and plunger seal 9060 asthey are pushed by the expansion of the biasing member 90122 from itsinitial energized state. The regulating mechanism 90500 does not drivethe delivery but only controls the delivery motion. The tether limits orotherwise restrains the motion of the piston 90110 and plunger seal9060, but does not apply the force for the delivery. According to apreferred embodiment, the controlled delivery drive mechanisms and drugdelivery devices of the present disclosure include a regulatingmechanism indirectly or directly connected to a tether metering theaxial translation of the piston 90110A, 90110B and plunger seal 9060,which are being driven to axially translate by the biasing member 90122.The rate of drug delivery as controlled by the regulating mechanism maybe determined by: selection of the gear ratio of gear assembly 90516;selection of the main/star gear 90102; selection of the diameter ofwinding drum/gear 90520; using electromechanical actuator 90101 tocontrol the rate of rotation of the main/star gear 90102; or any othermethod known to one skilled in the art. By using electromechanicalactuator 90101 the rate of rotation of the main/star gear 90102 it maybe possible to configure a drug delivery device to provide a variabledose rate (i.e., the rate of drug delivery is varied during atreatment).

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether 90525 by the winch drum/gear 90520 and thereby permitaxial translation of the piston 90110 by the biasing member 90122 totranslate a plunger seal 9060 within a barrel 9058. The one or moreinputs may be provided by the actuation of the activation mechanism, acontrol interface, and/or a remote control mechanism. The power andcontrol system may be configured to receive one or more inputs to adjustthe restraint provided by the tether 90525 and winch drum/gear 90520 onthe free axial translation of the piston 90110 upon which the biasingmember 90122 bears upon to meet a desired drug delivery rate or profile,to change the dose volume for delivery to the user, and/or to otherwisestart, stop, or pause operation of the drive mechanism.

The components of the drive mechanism 90100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9060 of the drug container 9050. Optionally, the drive mechanism90100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9060 to, for example,ensure that substantially the entire drug dose has been delivered to theuser. For example, the plunger seal 9060, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user.

The tether 90525 may have one or more status triggers, such aselectrical contacts, optical markings, or electromechanical pins orrecesses, which are capable of contacting or being recognized by astatus reader. In at least one embodiment, an end-of-dose statusindication may be provided to the user once the status reader contactsor recognizes the final status trigger positioned on the tether 90525that would contact the status reader at the end of axial travel of thepiston 90110A, 90110B and plunger 9060 within the barrel 9058 of thedrug container 9050. The status reader may be, for example, anelectrical switch reader to contact the corresponding electricalcontacts, an optical reader to recognize the corresponding opticalmarkings, or a mechanical or electromechanical reader configured tocontact corresponding pins, holes, or similar aspects on the tether. Thestatus triggers may be positioned along the tether 90525 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asthe drug delivery device is activated and drug delivery is begun byrelease of the biasing member 90122 and the resulting force applied tothe piston 90110A, 90110B and plunger seal 6900, the rate or profile ofdrug delivery to the user is controlled by the regulating mechanism90500, gear assembly 90516, and winch drum/gear 90520 releasing thetether 90525 and permitting expansion of the biasing member 90122 andaxial translation of the piston 90110A, 90110B and plunger seal 9060. Asthis occurs, the status triggers of the tether 90525 are contacted orrecognized by the status reader and the status of the drive mechanismbefore, during, and after operation can be relayed to the power andcontrol system to provide feedback to the user. Depending on the numberof status triggers located on the tether 90525, the frequency of theincremental status indication may be varied as desired. As describedabove, a range of status readers may be utilized depending on the statustriggers utilized by the system.

In a preferred embodiment, the status reader may apply a tensioningforce to the tether 90525. When the system reaches end-of-dose, thetether 90525 goes slack and the status reader 90544 is permitted torotate about a fulcrum. This rotation may operate an electrical orelectromechanical switch, for example a switch, signaling slack in thetether 90525 to the power and control system. Additionally, a gear 90511of gear assembly 90516 may act as an encoder along with a sensor. Thesensor/encoder combination is used to provide feedback of gear assemblyrotation, which in turn can be calibrated to the position of piston90110 when there is no slack in the tether 90525. Together, the statusreader and sensor/encoder may provide positional feedback, end-of-dosesignal, and error indication, such as an occlusion, by observing slackin the tether 90525 prior to reaching the expected number of motorrotations as counted by the sensor/encoder.

Additional means may exist for terminating or restraining the flow ofthe medicament in the case of slack in, or failure of, the tether. FIGS.74A-74B show one such embodiment. Disposed within barrel 9058 are brake9064, sleeve 9062, and plug 9068, and optionally retainer 9066. Biasingmember 90122 bears against sleeve 9062. Tether 90525 is engaged withplug 9068, thereby allowing tether 90525 to restrain the motion ofsleeve 9062. This restraint controls the rate of expansion orde-energizing of biasing member 90122. When tether 90525 is undertension, plug 9068 bears against distal face 9064A of brake 9064,causing proximal face 9064B of brake 9064 to bear against sleeve 9062.Due to this contact, and the profile of the distal end 9062A of sleeve9062, brake 9064 is maintained in a substantially conical configurationas shown in FIG. 74A. In this configuration, expansion or de-energizingof biasing member 90122 is restrained. Also, in this conicalconfiguration, the outer diameter of brake 9064 is less than the innerdiameter of barrel 9058, thus translation of the brake is not restrainedby contact with the inner wall of the drug container. Also, a portion ofbrake 9064 is in contact with retainer 9066. Because brake 9064 ismaintained in this configuration by plug 9068 and sleeve 9062,translation of sleeve 9062, caused by decompression of biasing member90122, is transferred to retainer 9066. Likewise, contact of retainer9066 with plunger seal 9060 causes translation of plunger seal 9060.

As shown in FIG. 74B, in the event of slack in, or failure of, tether90525, plug 9068 is no longer held in position by tether 90525 and,therefore, no longer restrains motion of sleeve 9062. As biasing member90122 decompresses or de-energizes, brake 9064 transforms to arelatively less conical or flatter configuration. This may be caused bya natural bias of brake 9064 to transform to this configuration or,alternatively, may be caused by contact of brake 9064 with both retainer9066 and sleeve 9062. As the brake is transformed, it comes into contactwith the inner wall of barrel 9058. The brake thus acts as a wedge torestrict translation of sleeve 9062. This may prevent furthertranslation or may act to restrict the rate of translation. Optionally,restoring tension in the tether may cause the plug to contact the brakeand to transform the brake back to its conical configuration and thusrestore normal operation of the drug delivery device.

FIGS. 74A-74B show the plug as having a spherical shape and the brake ashaving a conical shape. Such shapes are used herein merely for exemplarypurposes and other shapes or configurations could readily be utilized toachieve the same or similar functionality. For example, the plug mayitself be conical in shape and, in one embodiment, be shaped tointerface the brake when the brake is in a conical shape. In such aconfiguration, the conical shape of the plug assists in maintaining theconical shape of the brake, thereby preventing contact between the outerdiameter of the brake with the inner diameter of the barrel in order torestrict the axial translation of the sleeve 9062 (i.e., applying abraking force). In another embodiment, the brake 9064 could employ astar-shaped or other configuration when in a substantially flattenedposition so as to make contact with the inner diameter of the barrel9058 to prevent or restrict further axial translation of sleeve 9062.Without further translation of sleeve 9062, biasing member 90122 cannotexpand or de-energize further which, in turn, prevents or restrictsfurther drug delivery to the user. This provides a necessary and usefulsafety measure for drug delivery, to prevent over-delivery oraccelerated delivery of drug to the user.

Referring back to FIGS. 70A-70D and 71A-71D, in addition to controllingthe rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container (thereby deliveringdrug substances at variable rates and/or delivery profiles); themulti-function drive mechanisms of the present disclosure mayconcurrently or sequentially perform the steps of: triggering a needleinsertion mechanism to provide a fluid pathway for drug delivery to auser; and connecting a sterile fluid pathway to a drug container topermit fluid flow from the drug container to the needle insertionmechanism for delivery to the user. In at least one embodiment, as shownin FIGS. 70A-70D and 71A-71D, initial motion by the actuator 90101 ofthe multi-function drive mechanism 90100 causes rotation of main/stargear 90102. Main/star gear 90102 is shown as a compound gear withaspects 90102A and 90102B (see FIG. 72). In one manner, main/star gear90102 conveys motion to the regulating mechanism 90500 through gearassembly 90516. In another manner, main/star gear 90102 conveys motionto the needle insertion mechanism 90200 through gear 90112. As gear90112 is rotated by main/star gear 90102, gear 90112 engages the needleinsertion mechanism 90200 to initiate the fluid pathway connector intothe user, as described in detail above. In one particular embodiment,needle insertion mechanism 90200 is a rotational needle insertionmechanism. Accordingly, gear 90112 is configured to engage acorresponding gear surface 90208 of the needle insertion mechanism90200. Rotation of gear 90112 causes rotation of needle insertionmechanism 90200 through the gear interaction between gear 90112 of thedrive mechanism 90100 and corresponding gear surface 90208 of the needleinsertion mechanism 90200. Once suitable rotation of the needleinsertion mechanism 90200 occurs, for example rotation along axis ‘R’shown in FIG. 70B-70C, the needle insertion mechanism may be initiatedto create the fluid pathway connector into the user, as described indetail above. In an alternative embodiment, as shown in FIGS. 75A-75B,gear 90112 may indirectly engage the needle insertion mechanism 90200 toinitiate the fluid pathway connector into the user. For example, gear90112 may be configured to engage a corresponding gear surface of acontrol arm 90202 (visible in FIG. 75) that contacts or blocks theneedle insertion mechanism 90200. Rotation of gear 90112 causes movementof the control arm 90202, which may initiate or permit rotation ofneedle insertion mechanism 90200. Such a needle insertion mechanism, asshown in FIGS. 75A-75B, includes a rotationally biased member 90210which is initially held in an energized state. The rotational biasingmember may be prevented from de-energizing by contact of a component ofthe insertion mechanism with a rotation prevention feature, such as ablocking aspect of the control arm, of the drug delivery device. Uponactivation of the device, or another input, the rotationally biasedmember 90210 is permitted to, at least partially, de-energize. Thiscauses one or more components of the insertion mechanism to rotate and,in turn, cause, or allow, the insertion of the needle into the patient.Further, a cannula may be inserted into the patient as described above.At a later time, such as when the control arm or another component ofthe device recognizes a slack in the tether 90525, the rotationallybiased member may be allowed to further de-energize, such as by furtherinteraction with the control arm, causing additional rotation of one ormore components of the insertion mechanism. This rotation may cause, orallow, the needle to be retracted from the patient. The needle may befully retracted in a single step or there may be multiple steps ofretraction.

As shown in FIGS. 70A-70D and 71A-71D, rotation of the needle insertionmechanism 90200 in this manner may also cause a connection of a sterilefluid pathway to a drug container to permit fluid flow from the drugcontainer to the needle insertion mechanism for delivery to the user.Ramp aspect 90222 of needle insertion mechanism 90200 is caused to bearupon a movable connection hub 90322 of the sterile fluid pathwayconnector 90300. As the needle insertion mechanism 90200 is rotated bythe multi-function drive mechanism 90100, ramp aspect 90222 of needleinsertion mechanism 90200 bears upon and translates movable connectionhub 90322 of the sterile fluid pathway connector 90300 to facilitate afluid connection therein. Such translation may occur, for example, inthe direction of the hollow arrow along axis ‘C’ shown in FIGS. 70B and71B. In at least one embodiment, the needle insertion mechanism 90200may be configured such that a particular degree of rotation uponrotational axis ‘R’ (shown in FIGS. 70B-70C) enables the needle/trocarto retract as detailed above. Additionally or alternatively, suchneedle/trocar retraction may be configured to occur upon a user-activityor upon movement or function of another component of the drug deliverydevice. In at least one embodiment, needle/trocar retraction may beconfigured to occur upon end-of-drug-delivery, as triggered by, forexample, the regulating mechanism 90500 and/or one or more of the statusreaders as described above. During these stages of operation, deliveryof fluid substances from the drug chamber 9021 may be initiated,on-going, and/or completed by the expansion of the biasing member 90122from its initial energized state acting upon the piston 90110A, 90110Band plunger seal 60. As described above, the regulating mechanisms 90500function to provide resistance to the free motion of the piston 90110A,90110B and plunger seal 9060 as they are pushed by the expansion of thebiasing member 90122 from its initial energized state. The regulatingmechanism 90500 does not drive the delivery but only controls thedelivery motion. The tether limits or otherwise restrains the motion ofthe piston 90110 and plunger seal 9060, but does not apply the force forthe delivery. This is visible through the progression of the componentsshown in FIGS. 70A-70D and 71A-71D. The motion of the piston 90110A,90110B and plunger seal 9060 as they are pushed by the expansion of thebiasing member 90122 from its initial energized state are shown in thedirection of the solid arrow along axis ‘A’ from proximal or firstposition ‘P’ to the distal or second position ‘D’, as shown in thetransition of FIGS. 70A-70D and 71A-71D.

Further aspects of the novel drive mechanism will be described withreference to FIG. 72 and FIGS. 73A-73B. FIG. 72 shows a perspective viewof the multi-function drive mechanism, according to at least a firstembodiment, during its initial locked stage. Initially, the tether 90525may retain the biasing member 90122 in an initial energized positionwithin piston 90110A, 90110B. Directly or indirectly upon activation ofthe device by the user, the multi-function drive mechanism 90100 may beactivated to permit the biasing member to impart a force to piston 90110and therefore to tether 90525. This force on tether 90525 imparts atorque on winding drum 90520 which causes the gear assembly 90516 andregulating mechanism 90500 to begin motion. As shown in FIG. 73A, thepiston 90110 and biasing member 90122 are both initially in acompressed, energized state behind the plunger seal 60. The biasingmember 90122 may be maintained in this state until activation of thedevice between internal features of drive housing 90130 and interfacesurface 90110C of piston 90110A, 90110B. As the drug delivery device9010 is activated and the drive mechanism 90100 is triggered to operate,biasing member 90122 is permitted to expand (i.e., decompress) axiallyin the distal direction (i.e., in the direction of the solid arrow shownin FIGS. 70A-70D and FIGS. 71A-71D). Such expansion causes the biasingmember 90122 to act upon and distally translate interface surface 90110Cand piston 90110, thereby distally translating plunger seal 9060 to pushdrug fluid out of the drug chamber 9021 of barrel 9058. In at least oneembodiment, an end-of-dose status indication may be provided to the useronce the status reader contacts or recognizes a status triggerpositioned on the tether 90525 to substantially correspond with the endof axial travel of the piston 90110A, 90110B and plunger seal 9060within the barrel 9058 of the drug container 9050. The status triggersmay be positioned along the tether 90525 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the user. In at least one embodiment,the status reader is an optical status reader configured to recognizethe corresponding optical status triggers on the tether. As would beunderstood by an ordinarily skilled artisan, such optical statustriggers may be markings which are recognizable by the optical statusreader. In another embodiment, the status reader is a mechanical orelectromechanical reader configured to physically contact correspondingpins, holes, or similar aspects on the tether. Electrical contacts couldsimilarly be utilized on the tether as status indicators which contactor are otherwise recognized by the corresponding electrical statusreader. The status triggers may be positioned along the tether 90525 tobe read or recognized at positions which correspond with the beginningand end of drug delivery, as well as at desired increments during drugdelivery. As shown, tether 90525 passes substantially axially throughthe drive mechanism housing 90130, the biasing member 90122, andconnects to the piston 90110 A, 90110B to restrict the axial translationof the piston 90110A, 90110B and the plunger seal 9060 that residesadjacent thereto.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement ofwinding drum 90520 and, thus, axial translation of the components of thecontrolled delivery drive mechanism 90100. Accordingly, the regulatingmechanism 90500 only controls the motion of the drive mechanism, butdoes not apply the force for the drug delivery. One or more additionalbiasing members 90122, such as compression springs, may be utilized todrive or assist the driving of the piston 90110. For example, acompression spring may be utilized within the drive housing 90130 forthis purpose. The regulating mechanism 90500 only controls, meters, orregulates such action. The controlled delivery drive mechanisms and/ordrug delivery devices of the present disclosure may additionally enablea compliance push to ensure that substantially all of the drug substancehas been pushed out of the drug chamber 9021. The plunger seal 9060,itself, may have some compressibility permitting a compliance push ofdrug fluid from the drug container. For example, when a pop-out plungerseal is employed, i.e., a plunger seal that is deformable from aninitial state, the plunger seal may be caused to deform or “pop-out” toprovide a compliance push of drug fluid from the drug container.Additionally or alternatively, an electromechanical status switch andinterconnect assembly may be utilized to contact, connect, or otherwiseenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

In at least one embodiment, incremental status indication may beprovided to the user by reading or recognizing the rotational movementof one or more gears of gear assembly 90516. As the gear assembly 90516rotates, a status reader may read or recognize one or more correspondingstatus triggers on one of the gears in the gear assembly to provideincremental status indication before, during, and after operation of thevariable rate controlled delivery drive mechanism. A number of statusreaders may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism may utilize a mechanicalstatus reader which is physically contacted by gear teeth of one of thegears of the gear assembly. As the status reader is contacted by thestatus trigger(s), which in this exemplary embodiment may be the gearteeth of one of the gears (or holes, pins, ridges, markings, electricalcontacts, or the like, upon the gear), the status reader measures therotational position of the gear and transmits a signal to the power andcontrol system for status indication to the user. Additionally oralternatively, the drive mechanism may utilize an optical status reader.The optical status reader may be, for example, a light beam that iscapable of recognizing a motion and transmitting a signal to the powerand control system. For example, the drive mechanism may utilize anoptical status reader that is configured to recognize motion of the gearteeth of one of the gears in the gear assembly (or holes, pins, ridges,markings, electrical contacts, or the like, upon the gear). Similarly,the status reader may be an electrical switch configured to recognizeelectrical contacts on the gear. In any of these embodiments, the sensormay be utilized to then relay a signal to the power and control systemto provide feedback to the user.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to the user.While the drive mechanisms of the present disclosure are described withreference to the gear assembly and regulating mechanism shown in thefigures, a range of configurations may be acceptable and capable ofbeing employed within the embodiments of the present disclosure, aswould readily be appreciated by an ordinarily skilled artisan.Accordingly, the embodiments of the present disclosure are not limitedto the specific gear assembly and regulating mechanism described herein,which is provided as an exemplary embodiment of such mechanisms foremployment within the controlled delivery drive mechanisms and drugdelivery pumps.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of actuator 90101. The change in the rate of movementof actuator 90101 causes a change in the rotation rate of regulatingmechanism 90500 which, in turn, controls the rate of drug delivery tothe user. Alternatively, the delivery profile may be altered by a changein the characteristics of the flow path of medicament through theconduit connecting the drug container and insertion mechanism. Thechange may be caused by the introduction, removal, or modification of aflow restrictor which restricts flow of medicament from the drugcontainer to the insertion mechanism. For example, a flow restrictor mayhave multiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

Assembly and/or manufacturing of controlled delivery drive mechanism90100, drug delivery pump 9010, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9050 may first be assembledand filled with a fluid for delivery to the user. The drug container9050 includes a cap 9052, a pierceable seal 9056, a barrel 9058, and aplunger seal 9060. The pierceable seal 9056 may be fixedly engagedbetween the cap 9052 and the barrel 9058, at a distal end of the barrel9058. The barrel 9058 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9060 from theproximal end of the barrel 9058. An optional connection mount 9054 maybe mounted to a distal end of the pierceable seal 9056. The connectionmount 9054 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 58 of the drug container 9050. Thedrug container 9050 may then be mounted to a distal end of drive housing90130.

One or more drive biasing members 90122 may be inserted into a distalend of the drive housing 90130. Optionally, a cover sleeve 90140 may beinserted into a distal end of the drive housing 90130 to substantiallycover biasing member 90122. A piston may be inserted into the distal endof the drive housing 90130 such that it resides at least partiallywithin an axial pass-through of the biasing member 90122 and the biasingmember 90122 is permitted to contact a piston interface surface 90110Cof piston 90110A, 90110B at the distal end of the biasing member 90122.An optional cover sleeve 90140 may be utilized to enclose the biasingmember 90122 and contact the piston interface surface 90110C of piston90110A, 90110B. The piston 90110A, 90110B and drive biasing member90122, and optional cover sleeve 90140, may be compressed into drivehousing 90130. Such assembly positions the drive biasing member 90122 inan initial compressed, energized state and preferably places a pistoninterface surface 90110C in contact with the proximal surface of theplunger seal 9060 within the proximal end of barrel 9058. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 90130 prior to attachment or mounting of the drug container9050. The tether 90525 is pre-connected to the proximal end of thepiston 90110A, 90110B and passed through the axial aperture of thebiasing member 90122 and drive mechanism 90130, and then wound throughthe interior of the drug delivery device with the other end of thetether 90525 wrapped around the winch drum/gear 90520 of the regulatingmechanism 90500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 69B.

Certain optional standard components or variations of drive mechanism90100 or drug delivery device 9010 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9018 to enablethe user to view the operation of the drug delivery device 9010 orverify that drug dose has completed. Similarly, the drug delivery device9010 may contain an adhesive patch 9026 and a patch liner 9028 on thebottom surface of the housing 9012. The adhesive patch 9026 may beutilized to adhere the drug delivery device 9010 to the body of the userfor delivery of the drug dose. As would be readily understood by onehaving ordinary skill in the art, the adhesive patch 9026 may have anadhesive surface for adhesion of the drug delivery device to the body ofthe user. The adhesive surface of the adhesive patch 9026 may initiallybe covered by a non-adhesive patch liner 9028, which is removed from theadhesive patch 9026 prior to placement of the drug delivery device 9010in contact with the body of the user. Removal of the patch liner 9028may further remove the sealing membrane 90254 of the insertion mechanism90200, opening the insertion mechanism to the body of the user for drugdelivery (as shown in FIG. 69C).

Similarly, one or more of the components of controlled delivery drivemechanism 90100 and drug delivery device 9010 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9010 is shown as two separate components upper housing9012A and lower housing 9012B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The novel controlleddelivery drive mechanisms of the present disclosure may be directly orindirectly activated by the user. Furthermore, the novel configurationsof the controlled delivery drive mechanism and drug delivery devices ofthe present disclosure maintain the sterility of the fluid pathwayduring storage, transportation, and through operation of the device.Because the path that the drug fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe drug container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent disclosure do not require terminal sterilization upon completionof assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connector, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a user, wherein aregulating mechanism acting to restrain the distribution of a tether isutilized to meter the free axial translation of the piston. The methodof operation of the drive mechanism and the drug delivery device may bebetter appreciated with reference to FIGS. 70A-70D and FIGS. 71A-71D, asdescribed above.

In some embodiments, the power and control system 91810: (a) determinesoptimal temperature of the drug, appropriate time for delivery, etc.based on signals from an on-body sensor 91840, temperature sensor 91880,and/or other sensors; (b) sends command signals to the drive controlsystem 91820 for initiating drug delivery; (c) provides a “deliveryrate” information to the drive control system 91820; and (d) receives‘drug delivery information’ and transmits ‘end of delivery information’to a remote computing device via a communication unit 91830.

In some embodiments, the drive control system 91820: (a) drives themulti-function drive mechanism, such as the drive mechanism 90100,regulating mechanism 90500, needle insertion mechanism, connecting fluidpathway (see FIG. 78C); and (b) controls the regulating element 90500 orgear assembly.

In some embodiments, the controller may be included in the drive controlsystem 91820. The controller 91822 may drive the actuator/motor 90101based on the command signals received from the power and control system91810. The controller 91822 may translate the delivery rate informationinto: selection of gears, selection of diameters, rate of rotation,selection, etc. The controller 91822 may then drive the variouscomponents of the drive control system 91820 to deliver the drugaccording to the required “delivery rate (see FIG. 78B).

X. Other Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B and 33A-33C, may be configured to incorporate the embodiments ofthe drive mechanism described below in connection with FIGS. 69A-73D.The embodiments of the drive mechanism described below in connectionwith FIGS. 69A-73D may be used to replace, in its entirety or partially,the above-described drive mechanism 100, 6100, or 8100, or any otherdrive mechanism described herein, where appropriate.

The multi-function drive mechanisms of the present disclosure enable orinitiate several functions, including: (i) controlling the rate of drugdelivery by metering, providing resistance, or otherwise preventing freeaxial translation of the plunger seal utilized to force a drug substanceout of a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a patient; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the patient. With reference to the embodiments shown inFIGS. 70A-70D and 71A-71D, multi-function drive mechanism 90100 includesan actuator 90101, a gear assembly 90110 including a main gear 90102, adrive housing 90130, and a drug container 9050 having a cap 9052, apierceable seal (not visible), a barrel 9058, and a plunger seal 9060.The main gear 90102 may be, for example, a star gear disposed to contactmultiple secondary gears or gear surfaces. A drug chamber 9021, locatedwithin the barrel 9058 between the pierceable seal and the plunger seal9060, may contain a drug fluid for delivery through the insertionmechanism and drug delivery device into the body of the patient. Theseals described herein may be comprised of a number of materials butare, in a preferred embodiment, comprised of one or more elastomers orrubbers. The drive mechanism 90100 may further contain one or more drivebiasing members, one or more release mechanisms, and one or more guides,as are described further herein. The components of the drive mechanismfunction to force a fluid from the drug container out through thepierceable seal, or preferably through the piercing member of the fluidpathway connector, for delivery through the fluid pathway connector,sterile fluid conduit, and insertion mechanism into the body of thepatient.

In one particular embodiment, the drive mechanism 90100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the patient, the power and control systemmay be actuated to directly or indirectly release the compressionspring(s) from an energized state. Upon release, the compressionspring(s) may bear against and act upon the plunger seal to force thefluid drug out of the drug container. The compression spring may bearagainst and act upon a piston which, in turn, acts upon the plunger sealto force the fluid drug out of the drug container. The fluid pathwayconnector may be connected through the pierceable seal prior to,concurrently with, or after activation of the drive mechanism to permitfluid flow from the drug container, through the fluid pathway connector,sterile fluid conduit, and insertion mechanism, and into the body of thepatient for drug delivery. In at least one embodiment, the fluid flowsthrough only a manifold and a cannula of the insertion mechanism,thereby maintaining the sterility of the fluid pathway before and duringdrug delivery. Such components and their functions are described infurther detail herein.

Referring now to the embodiment of the multi-function drive mechanismshown in FIGS. 70A-70D and 70A-70D, multi-function drive mechanism 90100includes an actuator 90101, a gear assembly 90110 including a main gear90102, a drive housing 90130, and a drug container 9050 having a cap9052, a pierceable seal (not visible), a barrel 9058, and a plunger seal9060. The main gear 90102 may be, for example, a star gear disposed tocontact multiple secondary gears or gear surfaces. A drug chamber 9021,located within the barrel 9058 between the pierceable seal and theplunger seal 9060, may contain a drug fluid for delivery through theinsertion mechanism and drug delivery device into the body of thepatient. Compressed within the drive housing 90130, between the drugcontainer 9050 and the proximal end of the housing 90130, are one ormore drive biasing members 90122 and a piston 90110, wherein the drivebiasing members 90122 are configured to bear upon an interface surface90110C of the piston 90110, as described further herein. Optionally, acover sleeve (not shown) may be utilized between the drive biasingmembers 90122 and the interface surface 90110C of the piston 90110 to,for example, promote more even distribution of force from the drivebiasing member 90122 to the piston 90110, prevent buckling of the drivebiasing members 90122, and/or hide biasing members 90122 from patientview. Interface surface 90110C of piston 90110 is caused to restsubstantially adjacent to, or in contact with, a proximal end of seal9060. Although the embodiments shown in FIGS. 70A-70D and 71A-71D show asingular biasing member it is also contemplated that one or more biasingmembers disposed to act in parallel may be used.

As best shown in FIG. 70D and FIG. 71D, the piston 90110 may becomprised of two components 90110A and 90110B and have an interfacesurface 90110C to contact the plunger seal. A tether, ribbon, string, orother retention strap (referred to herein as the “tether” 90525) may beconnected at one end to the piston 90110A, 90110B. For example, thetether 90525 may be connected to the piston 90110A, 90110B by retentionbetween the two components of the piston 8110A, 8110B when assembled.The tether 8525 is connected at another end to a winch drum/gear 90520of a delivery control mechanism 90500. Through the use of the winchdrum/gear 90520 connected to one end of the tether 90525, and the tether90525 connected at another end to the piston 90110A, 90110B, theregulating mechanism 90500 functions to control, meter, provideresistance, or otherwise prevent free axial translation of the piston90110A, 90110B and plunger seal 9060 utilized to force a drug substanceout of a drug container 9050. Accordingly, the regulating mechanism90500 is a portion of the gear assembly 90116 aspect of themulti-function drive mechanism, which together function to control therate or profile of drug delivery to the patient.

As shown in FIGS. 70A-70D and 71A-71D, and in isolation in FIGS. 72 and73A-73B, in the embodiments of the present disclosure, the regulatingmechanism 90500 is gear assembly driven by an actuator 90101 of themulti-function drive mechanism 90100. The regulating mechanism retardsor restrains the distribution of tether 90525, only allowing it toadvance at a regulated or desired rate. This restricts movement ofpiston 90110 within barrel 9058, which is pushed by one or more biasingmembers 90122, hence controlling the movement of plunger seal 9060 anddelivery of the drug contained in chamber 9021. As the plunger seal 9060advances in the drug container 9050, the drug substance is dispensedthrough the sterile pathway connection 90300, conduit 9030, insertionmechanism 90200, and into the body of the patient for drug delivery. Theactuator 90101 may be a number of power/motion sources including, forexample, a solenoid, a stepper motor, or a rotational drive motor. In aparticular embodiment, the actuator 90101 is a rotational stepper motorwith a notch that corresponds with the gear teeth of the main/star gear90102. Commonly, such a rotational stepper motor may be referred to as a‘Pac-Man’ motor. In at least one embodiment, the Pac-Man motor has agear interface within which one or more teeth of the main gear maypartially reside during operation of the system. This is more clearlyvisible in FIGS. 73A-73B. When the gear interface 90101A of the Pac-Manmotor 90101 is in alignment with a tooth 90102A of the main gear 90102,rotational motion of the Pac-Man motor 90101 causes gear interfacerotation of the main gear 90102. When the Pac-Man motor 90101 is betweengear teeth of the main gear, it may act as a resistance for, forexample, back-spinning or unwinding of the gear assembly 90116. Furtherdetail about the gear assembly 90116, regulating mechanism 90500, andmulti-function drive mechanism 90100 are provided herein.

In a particular embodiment shown in FIGS. 73A-73B, the regulatingelement 90500 further includes one or more gears 90511, 90512, 90513,90514, of a gear assembly 90516. One or more of the gears 90511, 90512,90513, 90514 may be, for example, compound gears having a small diametergear attached at a shared center point to a large diameter gear. Gear90513 may be rotationally coupled to winch drum/gear 90520, for exampleby a keyed shaft, thereby coupling rotation of gear assembly 90516 towinch drum/gear 90520. Compound gear 90512 engages the small diametergear 90513 such that rotational movement of the compound gear aspect90512B is conveyed by engagement of the gears (such as by engagement ofcorresponding gear teeth) to gear 90513. Compound gear aspect 90512A,the rotation of which is coupled to gear aspect 90512B, is caused torotate by action of compound gear aspect 90102B of the main/star gear90102. Compound gear aspect 90102B, the rotation of which is coupled tomain/star gear 90102, is caused to rotate by interaction betweenmain/star gear 90102A and interface 90101A of the actuator 90101. Thus,rotation of main/star gear 90102 is conveyed to winch drum/gear 90520.Accordingly, rotation of the gear assembly 90516 initiated by theactuator 90101 may be coupled to winch drum/gear 90520 (i.e., throughthe gear assembly 90516), thereby controlling the distribution of tether90525, and the rate of movement of plunger seal 9060 within barrel 9058to force a fluid from drug chamber 9021. The rotational movement of thewinch drum/gear 90520, and thus the axial translation of the piston90110 and plunger seal 9060, are metered, restrained, or otherwiseprevented from free axial translation by other components of theregulating element 90500, as described herein. As described above, theactuator 90101 may be a number of known power/motion sources including,for example, a motor (e.g., a DC motor, AC motor, or stepper motor) or asolenoid (e.g., linear solenoid, rotary solenoid).

Notably, the regulating mechanisms 90500 of the present disclosure donot drive the delivery of fluid substances from the drug chamber 9021.The delivery of fluid substances from the drug chamber 9021 is caused bythe expansion of the biasing member 90122 from its initial energizedstate acting upon the piston 90110A, 90110B and plunger seal 9060. Theregulating mechanisms 90500 instead function to provide resistance tothe free motion of the piston 90110A, 90110B and plunger seal 9060 asthey are pushed by the expansion of the biasing member 90122 from itsinitial energized state. The regulating mechanism 90500 does not drivethe delivery but only controls the delivery motion. The tether limits orotherwise restrains the motion of the piston 90110 and plunger seal9060, but does not apply the force for the delivery. According to apreferred embodiment, the controlled delivery drive mechanisms and drugdelivery devices of the present disclosure include a regulatingmechanism indirectly or directly connected to a tether metering theaxial translation of the piston 90110A, 90110B and plunger seal 9060,which are being driven to axially translate by the biasing member 90122.The rate of drug delivery as controlled by the regulating mechanism maybe determined by: selection of the gear ratio of gear assembly 90516;selection of the main/star gear 90102; selection of the diameter ofwinding drum/gear 90520; using electromechanical actuator 90101 tocontrol the rate of rotation of the main/star gear 90102; or any othermethod known to one skilled in the art. By using electromechanicalactuator 90101 the rate of rotation of the main/star gear 90102 it maybe possible to configure a drug delivery device to provide a variabledose rate (i.e., the rate of drug delivery is varied during atreatment).

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether 90525 by the winch drum/gear 90520 and thereby permitaxial translation of the piston 90110 by the biasing member 90122 totranslate a plunger seal 9060 within a barrel 9058. The one or moreinputs may be provided by the actuation of the activation mechanism, acontrol interface, and/or a remote control mechanism. The power andcontrol system may be configured to receive one or more inputs to adjustthe restraint provided by the tether 90525 and winch drum/gear 90520 onthe free axial translation of the piston 90110 upon which the biasingmember 90122 bears upon to meet a desired drug delivery rate or profile,to change the dose volume for delivery to the patient, and/or tootherwise start, stop, or pause operation of the drive mechanism.

The components of the drive mechanism 90100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9060 of the drug container 9050. Optionally, the drive mechanism8100 may include one or more compliance features which enable additionalaxial translation of the plunger seal 9060 to, for example, ensure thatsubstantially the entire drug dose has been delivered to the patient.For example, the plunger seal 9060, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe patient. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the patient during use of the device.For example, the patient may be provided an initial feedback to identifythat the system is operational and ready for drug delivery. Uponactivation, the system may then provide one or more drug delivery statusindications to the patient. At completion of drug delivery, the drivemechanism and drug delivery device may provide an end-of-doseindication. As the end-of-dose indication is tied to the piston reachingthe end of its axial translation, the drive mechanism and drug deliverydevice provide a true end-of-dose indication to the patient.

The tether 90525 may have one or more status triggers, such aselectrical contacts, optical markings, or electromechanical pins orrecesses, which are capable of contacting or being recognized by astatus reader. In at least one embodiment, an end-of-dose statusindication may be provided to the patient once the status readercontacts or recognizes the final status trigger positioned on the tether90525 that would contact the status reader at the end of axial travel ofthe piston 90110A, 90110B and plunger 9060 within the barrel 8058 of thedrug container 9050. The status reader may be, for example, anelectrical switch reader to contact the corresponding electricalcontacts, an optical reader to recognize the corresponding opticalmarkings, or a mechanical or electromechanical reader configured tocontact corresponding pins, holes, or similar aspects on the tether. Thestatus triggers may be positioned along the tether 90525 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asthe drug delivery device is activated and drug delivery is begun byrelease of the biasing member 90122 and the resulting force applied tothe piston 90110A, 90110B and plunger seal 9060, the rate or profile ofdrug delivery to the patient is controlled by the regulating mechanism90500, gear assembly 90516, and winch drum/gear 90520 releasing thetether 90525 and permitting expansion of the biasing member 90122 andaxial translation of the piston 90110A, 90110B and plunger seal 9060. Asthis occurs, the status triggers of the tether 8525 are contacted orrecognized by the status reader and the status of the drive mechanismbefore, during, and after operation can be relayed to the power andcontrol system to provide feedback to the patient. Depending on thenumber of status triggers located on the tether 90525, the frequency ofthe incremental status indication may be varied as desired. As describedabove, a range of status readers may be utilized depending on the statustriggers utilized by the system.

In a preferred embodiment, the status reader may apply a tensioningforce to the tether 90525. When the system reaches end-of-dose, thetether 90525 goes slack and the status reader 90544 is permitted torotate about a fulcrum. This rotation may operate an electrical orelectromechanical switch, for example a switch, signaling slack in thetether 90525 to the power and control system. Additionally, a gear 90511of gear assembly 90516 may act as an encoder along with a sensor. Thesensor/encoder combination is used to provide feedback of gear assemblyrotation, which in turn can be calibrated to the position of piston90110 when there is no slack in the tether 90525. Together, the statusreader and sensor/encoder may provide positional feedback, end-of-dosesignal, and error indication, such as an occlusion, by observing slackin the tether 90525 prior to reaching the expected number of motorrotations as counted by the sensor/encoder.

Referring back to FIGS. 70A-70D and 71A-71D, in addition to controllingthe rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container (thereby deliveringdrug substances at variable rates and/or delivery profiles); themulti-function drive mechanisms of the present disclosure mayconcurrently or sequentially perform the steps of: triggering a needleinsertion mechanism to provide a fluid pathway for drug delivery to apatient; and connecting a sterile fluid pathway to a drug container topermit fluid flow from the drug container to the needle insertionmechanism for delivery to the patient. In at least one embodiment, asshown in FIGS. 70A-70D and 71A-71D, initial motion by the actuator 90101of the multi-function drive mechanism 90100 causes rotation of main/stargear 90102. Main/star gear 90102 is shown as a compound gear withaspects 90102A and 90102B (see FIG. 72). In one manner, main/star gear90102 conveys motion to the regulating mechanism 90500 through gearassembly 90516. In another manner, main/star gear 90102 conveys motionto the needle insertion mechanism 90200 through gear 90112. As gear90112 is rotated by main/star gear 90102, gear 90112 engages the needleinsertion mechanism 90200 to initiate the fluid pathway connector intothe patient, as described in detail above. In one particular embodiment,needle insertion mechanism 90200 is a rotational needle insertionmechanism. Accordingly, gear 90112 is configured to engage acorresponding gear surface 90208 of the needle insertion mechanism90200. Rotation of gear 90112 causes rotation of needle insertionmechanism 90200 through the gear interaction between gear 90112 of thedrive mechanism 90100 and corresponding gear surface 90208 of the needleinsertion mechanism 90200. Once suitable rotation of the needleinsertion mechanism 90200 occurs, for example rotation along axis ‘R’shown in FIG. 70B-70C, the needle insertion mechanism may be initiatedto create the fluid pathway connector into the patient, as described indetail above.

As shown in FIGS. 70A-70D and 71A-71D, rotation of the needle insertionmechanism 90200 in this manner may also cause a connection of a sterilefluid pathway to a drug container to permit fluid flow from the drugcontainer to the needle insertion mechanism for delivery to the patient.Ramp aspect 90222 of needle insertion mechanism 90200 is caused to bearupon a movable connection hub 322 of the sterile fluid pathway connector90300. As the needle insertion mechanism 90200 is rotated by themulti-function drive mechanism 90100, ramp aspect 90222 of needleinsertion mechanism 90200 bears upon and translates movable connectionhub 322 of the sterile fluid pathway connector 90300 to facilitate afluid connection therein. Such translation may occur, for example, inthe direction of the hollow arrow along axis ‘C’ shown in FIGS. 70B and71B. In at least one embodiment, the needle insertion mechanism 90200may be configured such that a particular degree of rotation uponrotational axis ‘R’ (shown in FIGS. 70B-70C) enables the needle/trocarto retract as detailed above. Additionally or alternatively, suchneedle/trocar retraction may be configured to occur upon apatient-activity or upon movement or function of another component ofthe drug delivery device. In at least one embodiment, needle/trocarretraction may be configured to occur upon end-of-drug-delivery, astriggered by, for example, the regulating mechanism 90500 and/or one ormore of the status readers as described above. During these stages ofoperation, delivery of fluid substances from the drug chamber 9021 maybe initiated, on-going, and/or completed by the expansion of the biasingmember 90122 from its initial energized state acting upon the piston90110A, 90110B and plunger seal 9060. As described above, the regulatingmechanisms 90500 function to provide resistance to the free motion ofthe piston 90110A, 90110B and plunger seal 9060 as they are pushed bythe expansion of the biasing member 90122 from its initial energizedstate. The regulating mechanism 90500 does not drive the delivery butonly controls the delivery motion. The tether limits or otherwiserestrains the motion of the piston 90110 and plunger seal 9060, but doesnot apply the force for the delivery. This is visible through theprogression of the components shown in FIGS. 70A-70D and 71A-71D. Themotion of the piston 90110A, 90110B and plunger seal 9060 as they arepushed by the expansion of the biasing member 90122 from its initialenergized state are shown in the direction of the solid arrow along axis‘A’ from proximal or first position ‘P’ to the distal or second position‘D’, as shown in the transition of FIGS. 70A-70D and 71A-71D.

Further aspects of the novel drive mechanism will be described withreference to FIG. 72 and FIGS. 73A-73B. FIG. 4 shows a perspective viewof the multi-function drive mechanism, according to at least a firstembodiment, during its initial locked stage. Initially, the tether 90525may retain the biasing member 90122 in an initial energized positionwithin piston 90110A, 90110B. Directly or indirectly upon activation ofthe device by the patient, the multi-function drive mechanism 90100 maybe activated to permit the biasing member to impart a force to piston90110 and therefore to tether 90525. This force on tether 90525 impartsa torque on winding drum 90520 which causes the gear assembly 90516 andregulating mechanism 90500 to begin motion. As shown in FIG. 73A, thepiston 90110 and biasing member 90122 are both initially in acompressed, energized state behind the plunger seal 9060. The biasingmember 90122 may be maintained in this state until activation of thedevice between internal features of drive housing 90130 and interfacesurface 90110C of piston 90110A, 90110B. As the drug delivery device9010 is activated and the drive mechanism 90100 is triggered to operate,biasing member 90122 is permitted to expand (i.e., decompress) axiallyin the distal direction (i.e., in the direction of the solid arrow shownin FIGS. 70A-70D and FIGS. 71A-71D). Such expansion causes the biasingmember 90122 to act upon and distally translate interface surface 90110Cand piston 90110, thereby distally translating plunger seal 9060 to pushdrug fluid out of the drug chamber 9021 of barrel 9058. In at least oneembodiment, an end-of-dose status indication may be provided to thepatient once the status reader contacts or recognizes a status triggerpositioned on the tether 90525 to substantially correspond with the endof axial travel of the piston 90110A, 90110B and plunger seal 9060within the barrel 9058 of the drug container 9050. The status triggersmay be positioned along the tether 90525 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the patient. In at least oneembodiment, the status reader is an optical status reader configured torecognize the corresponding optical status triggers on the tether. Aswould be understood by an ordinarily skilled artisan, such opticalstatus triggers may be markings which are recognizable by the opticalstatus reader. In another embodiment, the status reader is a mechanicalor electromechanical reader configured to physically contactcorresponding pins, holes, or similar aspects on the tether. Electricalcontacts could similarly be utilized on the tether as status indicatorswhich contact or are otherwise recognized by the correspondingelectrical status reader. The status triggers may be positioned alongthe tether 90525 to be read or recognized at positions which correspondwith the beginning and end of drug delivery, as well as at desiredincrements during drug delivery. As shown, tether 90525 passessubstantially axially through the drive mechanism housing 90130, thebiasing member 90122, and connects to the piston 90110A, 90110B torestrict the axial translation of the piston 90110A, 90110B and theplunger seal 9060 that resides adjacent thereto.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement ofwinding drum 90520 and, thus, axial translation of the components of thecontrolled delivery drive mechanism 90100. Accordingly, the regulatingmechanism 90500 only controls the motion of the drive mechanism, butdoes not apply the force for the drug delivery. One or more additionalbiasing members 90122, such as compression springs, may be utilized todrive or assist the driving of the piston 90110. For example, acompression spring may be utilized within the drive housing 90130 forthis purpose. The regulating mechanism 90500 only controls, meters, orregulates such action. The controlled delivery drive mechanisms and/ordrug delivery devices of the present disclosure may additionally enablea compliance push to ensure that substantially all of the drug substancehas been pushed out of the drug chamber 9021. The plunger seal 9060,itself, may have some compressibility permitting a compliance push ofdrug fluid from the drug container. For example, when a pop-out plungerseal is employed, i.e., a plunger seal that is deformable from aninitial state, the plunger seal may be caused to deform or “pop-out” toprovide a compliance push of drug fluid from the drug container.Additionally or alternatively, an electromechanical status switch andinterconnect assembly may be utilized to contact, connect, or otherwiseenable a transmission to the power and control system to signalend-of-dose to the patient. This configuration further enables trueend-of-dose indication to the patient.

In at least one embodiment, incremental status indication may beprovided to the patient by reading or recognizing the rotationalmovement of one or more gears of gear assembly 90516. As the gearassembly 90516 rotates, a status reader may read or recognize one ormore corresponding status triggers on one of the gears in the gearassembly to provide incremental status indication before, during, andafter operation of the variable rate controlled delivery drivemechanism. A number of status readers may be utilized within theembodiments of the present disclosure. For example, the drive mechanismmay utilize a mechanical status reader which is physically contacted bygear teeth of one of the gears of the gear assembly. As the statusreader is contacted by the status trigger(s), which in this exemplaryembodiment may be the gear teeth of one of the gears (or holes, pins,ridges, markings, electrical contacts, or the like, upon the gear), thestatus reader measures the rotational position of the gear and transmitsa signal to the power and control system for status indication to thepatient. Additionally or alternatively, the drive mechanism may utilizean optical status reader. The optical status reader may be, for example,a light beam that is capable of recognizing a motion and transmitting asignal to the power and control system. For example, the drive mechanismmay utilize an optical status reader that is configured to recognizemotion of the gear teeth of one of the gears in the gear assembly (orholes, pins, ridges, markings, electrical contacts, or the like, uponthe gear). Similarly, the status reader may be an electrical switchconfigured to recognize electrical contacts on the gear. In any of theseembodiments, the sensor may be utilized to then relay a signal to thepower and control system to provide feedback to the patient.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to thepatient. While the drive mechanisms of the present disclosure aredescribed with reference to the gear assembly and regulating mechanismshown in the Figures, a range of configurations may be acceptable andcapable of being employed within the embodiments of the presentdisclosure, as would readily be appreciated by an ordinarily skilledartisan. Accordingly, the embodiments of the present disclosure are notlimited to the specific gear assembly and regulating mechanism describedherein, which is provided as an exemplary embodiment of such mechanismsfor employment within the controlled delivery drive mechanisms and drugdelivery pumps.

Assembly and/or manufacturing of controlled delivery drive mechanism90100, drug delivery drug delivery device 9010, or any of the individualcomponents may utilize a number of known materials and methodologies inthe art. For example, a number of known cleaning fluids such asisopropyl alcohol and hexane may be used to clean the components and/orthe devices. A number of known adhesives or glues may similarly beemployed in the manufacturing process. Additionally, knownsiliconization and/or lubrication fluids and processes may be employedduring the manufacture of the novel components and devices. Furthermore,known sterilization processes may be employed at one or more of themanufacturing or assembly stages to ensure the sterility of the finalproduct.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9050 may first be assembledand filled with a fluid for delivery to the patient. The drug container9050 includes a cap 9052, a pierceable seal 9056, a barrel 9058, and aplunger seal 9060. The pierceable seal 9056 may be fixedly engagedbetween the cap 9052 and the barrel 9058, at a distal end of the barrel9058. The barrel 9058 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9060 from theproximal end of the barrel 9058. An optional connection mount 9054 maybe mounted to a distal end of the pierceable seal 9056. The connectionmount 9054 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9058 of the drug container 9050. Thedrug container 9050 may then be mounted to a distal end of drive housing90130.

One or more drive biasing members 90122 may be inserted into a distalend of the drive housing 90130. Optionally, a cover sleeve 90140 may beinserted into a distal end of the drive housing 90130 to substantiallycover biasing member 90122. A piston may be inserted into the distal endof the drive housing 90130 such that it resides at least partiallywithin an axial pass-through of the biasing member 90122 and the biasingmember 90122 is permitted to contact a piston interface surface 90110Cof piston 90110A, 90110B at the distal end of the biasing member 90122.An optional cover sleeve 90140 may be utilized to enclose the biasingmember 90122 and contact the piston interface surface 90110C of piston90110A, 90110B. The piston 90110A, 90110B and drive biasing member90122, and optional cover sleeve 90140, may be compressed into drivehousing 90130. Such assembly positions the drive biasing member 90122 inan initial compressed, energized state and preferably places a pistoninterface surface 90110C in contact with the proximal surface of theplunger seal 9060 within the proximal end of barrel 9058. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 90130 prior to attachment or mounting of the drug container9050. The tether 90525 is pre-connected to the proximal end of thepiston 90110A, 90110B and passed through the axial aperture of thebiasing member 90122 and drive mechanism 90130, and then wound throughthe interior of the drug delivery device with the other end of thetether 90525 wrapped around the winch drum/gear 90520 of the regulatingmechanism 90500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a patient.The components which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 69B.

Certain optional standard components or variations of drive mechanism90100 or drug delivery device 9010 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 18 to enable thepatient to view the operation of the drug delivery device 9010 or verifythat drug dose has completed. Similarly, the drug delivery device 9010may contain an adhesive patch 9026 and a patch liner 9028 on the bottomsurface of the housing 9012. The adhesive patch 9026 may be utilized toadhere the drug delivery device 9010 to the body of the patient fordelivery of the drug dose. As would be readily understood by one havingordinary skill in the art, the adhesive patch 9026 may have an adhesivesurface for adhesion of the drug delivery device to the body of thepatient. The adhesive surface of the adhesive patch 9026 may initiallybe covered by a non-adhesive patch liner 9028, which is removed from theadhesive patch 9026 prior to placement of the drug delivery device 9010in contact with the body of the patient. Removal of the patch liner 9028may further remove the sealing membrane 254 of the insertion mechanism90200, opening the insertion mechanism to the body of the patient fordrug delivery (as shown in FIG. 69C). In some embodiments, removal ofthe patch liner 9028 may also wake-up onboard electronics (e.g., thepower and control system 2400) by supplying them with electricity froman onboard battery.

Similarly, one or more of the components of controlled delivery drivemechanism 90100 and drug delivery device 9010 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9010 is shown as two separate components upper housing9012A and lower housing 9012B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to thepatient before, during, and after drug delivery. For example, thepatient may be provided an initial feedback to identify that the systemis operational and ready for drug delivery. Upon activation, the systemmay then provide one or more drug delivery status indications to thepatient. At completion of drug delivery, the drive mechanism and drugdelivery device may provide an end-of-dose indication. The novelcontrolled delivery drive mechanisms of the present disclosure may bedirectly or indirectly activated by the patient. Furthermore, the novelconfigurations of the controlled delivery drive mechanism and drugdelivery devices of the present disclosure maintain the sterility of thefluid pathway during storage, transportation, and through operation ofthe device. Because the path that the drug fluid travels within thedevice is entirely maintained in a sterile condition, only thesecomponents need be sterilized during the manufacturing process. Suchcomponents include the drug container of the drive mechanism, the fluidpathway connector, the sterile fluid conduit, and the insertionmechanism. In at least one embodiment of the present disclosure, thepower and control system, the assembly platform, the control arm, theactivation mechanism, the housing, and other components of the drugdelivery device do not need to be sterilized. This greatly improves themanufacturability of the device and reduces associated assembly costs.Accordingly, the devices of the present disclosure do not requireterminal sterilization upon completion of assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts thepatient during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a patient, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connector, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a patient, wherein aregulating mechanism acting to restrain the distribution of a tether isutilized to meter the free axial translation of the piston. The methodof operation of the drive mechanism and the drug delivery device may bebetter appreciated with reference to FIGS. 70A-70D and FIGS. 71A-71D, asdescribed above.

XI. Other Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, and 69A-73D may be configured to incorporate theembodiments of the drive mechanism described below in connection withFIGS. 80A-85C. The embodiments of the drive mechanism described below inconnection with FIGS. 80A-85C may be used to replace, in its entirety orpartially, the above-described drive mechanism 100, 6100, 8100, or 9010,or any other drive mechanism described herein, where appropriate.

The present disclosure provides drive mechanisms for the controlleddelivery of drug substances, drug delivery pumps with controlleddelivery drive mechanisms, the methods of operating such devices, andthe methods of assembling such devices. Notably, the drive mechanisms ofthe present disclosure control the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer. The novel embodiments of the present disclosure thus arecapable of delivering drug substances at variable rates. The controlleddelivery drive mechanisms of the present disclosure may bepre-configurable or dynamically configurable, such as by control by thepower and control system, to meet desired delivery rates or profiles, asexplained in detail below. Additionally, the drive mechanisms of thepresent disclosure provide integrated status indication features whichprovide feedback to the user before, during, and after drug delivery.For example, the user may be provided an initial feedback to identifythat the system is operational and ready for drug delivery. Uponactivation, the system may then provide one or more drug delivery statusindications to the user. At completion of drug delivery, the drivemechanism and drug delivery device may provide an end-of-doseindication. Because the end-of-dose indication is related to thephysical end of axial translation of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the novel devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a controlleddelivery drive mechanism which includes a drive housing, a piston, andone or more biasing members, wherein the one or more biasing members areinitially retained in an energized state and is configured to bear uponan interface surface of the piston. The piston is configured totranslate substantially axially within a drug container having a plungerseal and a barrel. A tether is connected at one end to the piston and atanother end to a winch drum of a regulating mechanism, wherein thetether restrains the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon. The drug container may containa drug fluid within a drug chamber for delivery to a user. Optionally, acover sleeve may be utilized between the biasing member and theinterface surface of the piston to hide the interior components of thebarrel (namely, the piston and the biasing member) from view duringoperation of the drive mechanism. The tether is configured to bereleased from a winch drum of the regulating mechanism to meter the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon.

In at least one embodiment, the regulating mechanism is an escapementregulating mechanism coupled to, or acting with, the winch drum. Theescapement regulating mechanism may further include a gear train havingone or more gears, wherein the rotation of at least one gear of the geartrain is coupled to the rotation of the winch drum. In a particularembodiment, the escapement regulating mechanism further includes a leverand an escape wheel configured to engage and meter the rotationalmovement of the gear train. The lever has pins and a prong, wherein theprong movably engages a post and is configured to removably engage animpulse pin of a balance wheel, and wherein the balance wheel engagesand is capable of oscillating around a post in combination with a hairspring. An electromechanical actuator such as a motor or solenoid mayadditionally be used to control the oscillation and/or rotation of thebalance wheel. For example, a DC or stepper motor may be used, or alinear or rotary solenoid may be used. The escape wheel is a compoundgear having escape teeth around the circumference of a large diameterescape gear and a small diameter gear configured to engage and meter thegear train. The metering of the gear train and/or winch drum by anescapement regulating mechanism controls the rate or profile of drugdelivery to a user.

The gear train may include a winch gear coupled to a winch drum uponwhich the tether may be releasably wound. The winch gear may beconfigured to engage a first compound gear, such that rotation of thewinch gear and the small gear of the first compound gear are linked. Thegear assembly may additionally include a second compound gear, whereinthe large gear of the first compound gear is engaged with the small gearof the second compound gear. The large gear of the second compound gearmay be engaged with a gear of the escape wheel such that rotation of thesecond compound gear and escape wheel are coupled. In this way rotationof the escape wheel is coupled to rotation of the winch drum and canthereby control the release of the tether from the winch drum to meterthe free expansion of the biasing member from its initial energizedstate and the free axial translation of the piston upon which thebiasing member bears upon. The metering of the tether by the regulatingmechanism controls the rate or profile of drug delivery to a user. Thepiston may be one or more parts and connects to a distal end of thetether.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug delivery pump having ahousing and an assembly platform, upon which an activation mechanism, aninsertion mechanism, a fluid pathway connector, a power and controlsystem, and a controlled delivery drive mechanism may be mounted, saiddrive mechanism having a drive housing, a piston, and a biasing member,wherein the biasing member is initially retained in an energized stateand is configured to bear upon an interface surface of the piston. Thepiston is configured to translate substantially axially within a drugcontainer having a plunger seal and a barrel. A tether is connected atone end to the piston and at another end to a winch drum of a deliveryregulating mechanism, wherein the tether restrains the free expansion ofthe biasing member from its initial energized state and the free axialtranslation of the piston upon which the biasing member bears upon. Thedrug container may contain a drug fluid within a drug chamber fordelivery to a user. Optionally, a cover sleeve may be utilized betweenthe biasing member and the interface surface of the piston to hide theinterior components of the barrel (namely, the piston and the biasingmember) from view during operation of the drive mechanism. The tether isconfigured to be released from a winch drum of the delivery regulatingmechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum upon which the tether may be releasably wound, rotation ofthe winch drum releases the tether from the winch drum to meter the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The metering of the tether controls the rate or profile of drugdelivery to a user. The piston may be one or more parts and connects toa distal end of the tether. The winch drum is coupled to a regulatingmechanism which controls rotation of the winch drum and hence meteringof the translation of the piston.

The drug delivery device may utilize the regulating mechanism describedabove in the first embodiment, which configuration utilizes anescapement regulating mechanism to control the metering of the tether.The escapement regulating mechanism may further include a gear trainhaving one or more gears. In a particular embodiment, the escapementregulating mechanism further includes a lever and an escape wheelconfigured to engage and meter the rotational movement of the geartrain. The lever has pins and a prong, wherein the prong movably engagesa post and is configured to removably engage an impulse pin of a balancewheel, and wherein the balance wheel engages and is capable ofoscillating around a post in combination with a hair spring. A motor,such as a DC motor or stepper motor, or a linear or rotary solenoid mayadditionally be used to control the oscillation and/or rotation of thebalance wheel. The escape wheel is a compound gear having escape teetharound the circumference of a large diameter escape gear and a smalldiameter gear configured to engage and meter the gear train. Themetering of the gear train by an escapement regulating mechanismcontrols the rate or profile of drug delivery to a user. The piston isconfigured to contact and axially translate the plunger seal within thebarrel.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch drum and thereby permit axial translation ofthe piston by the biasing member to translate a plunger seal within abarrel. The one or more inputs may be provided by the actuation of theactivation mechanism, a control interface, and/or a remote controlmechanism. The power and control system may be configured to receive oneor more inputs to adjust the restraint provided by the tether and winchdrum on the free axial translation of the piston upon which the biasingmember bears upon to meet a desired drug delivery rate or profile, tochange the dose volume for delivery to the user, and/or to otherwisestart, stop, or pause operation of the drive mechanism.

The novel embodiments of the present disclosure provide drive mechanismswhich are capable of metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thereby, controlling therate of delivery of drug substances. The novel control delivery drivemechanisms are additionally capable of providing the incremental statusof the drug delivery before, during, and after operation of the device.As will be described further below, the embodiments of the presentdisclosure may include one or more additional components which may beconsidered standard components in the industry of medical devices. Forexample, the embodiments may include one or more batteries utilized topower the motor, drive mechanisms, and drug delivery devices of thepresent disclosure. The components, and the embodiments containing suchcomponents, are within the contemplation of the present disclosure andare to be understood as falling within the breadth and scope of thepresent disclosure.

The present disclosure provides drive mechanisms for the controlleddelivery of drug substances and drug delivery pumps which incorporatesuch controlled delivery drive mechanisms. The drive mechanisms of thepresent disclosure control the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer and, thus, are capable of delivering drug substances atvariable rates and/or delivery profiles. Additionally, the drivemechanisms of the present disclosure provide integrated statusindication features which provide feedback to the user before, during,and after drug delivery. For example, the user may be provided aninitial feedback to identify that the system is operational and readyfor drug delivery. Upon activation, the system may then provide one ormore drug delivery status indications to the user. At completion of drugdelivery, the drive mechanism and drug delivery device may provide anend-of-dose indication.

The novel devices of the present disclosure provide drive mechanismswith integrated status indication and drug delivery pumps whichincorporate such drive mechanisms. Such devices are safe and easy touse, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. The novel devices of the presentdisclosure provide these desirable features without any of the problemsassociated with known prior art devices. Certain non-limitingembodiments of the novel drug delivery pumps, drive mechanisms, andtheir respective components are described further herein with referenceto the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.80A-80C show an exemplary drug delivery device according to at least oneembodiment of the present disclosure. The drug delivery device may beutilized to administer delivery of a drug treatment into a body of auser. As shown in FIGS. 80A-80C, the drug delivery device 9210 includesa pump housing 9212. Pump housing 9212 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug delivery device. Forexample, drug delivery device 9210 includes a pump housing 9212 whichincludes an upper housing 9212A and a lower housing 9212B. The drugdelivery device may further include an activation mechanism 9214, astatus indicator 9216, and a window 9218. Window 9218 may be anytranslucent or transmissive surface through which the operation of thedrug delivery device may be viewed. As shown in FIG. 80B, drug deliverydevice 9210 further includes assembly platform 9220, sterile fluidconduit 9230, drive mechanism 92100 having drug container 9250,insertion mechanism 92200, fluid pathway connector 92300, and a powerand control system (not shown). One or more of the components of suchdrug delivery devices may be modular in that they may be, for example,pre-assembled as separate components and configured into position ontothe assembly platform 9220 of the drug delivery device 9210 duringmanufacturing.

The pump housing 9212 contains all of the device components and providesa means of removably attaching the device 9210 to the skin of the user.The pump housing 9212 also provides protection to the interiorcomponents of the device 9210 against environmental influences. The pumphousing 9212 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9212 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9212 may include certaincomponents, such as status indicator 9216 and window 9218, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9210 provides anactivation mechanism 9214 that is displaced by the user to trigger thestart command to the power and control system. In a preferredembodiment, the activation mechanism is a start button 9214 that islocated through the pump housing 9212, such as through an aperturebetween upper housing 9212A and lower housing 9212B, and which contactsa control arm 40 of the power and control system. In at least oneembodiment, the start button 14 may be a push button, and in otherembodiments, may be an on/off switch, a toggle, or any similaractivation feature known in the art. The pump housing 9212 also providesa status indicator 16 and a window 9218. In other embodiments, one ormore of the activation mechanism 9214, the status indicator 9216, thewindow 9218, and combinations thereof may be provided on the upperhousing 9212A or the lower housing 9212B such as, for example, on a sidevisible to the user when the drug delivery device 9210 is placed on thebody of the user. Housing 9212 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device 9210 is configured such that, upon activation by auser by depression of the activation mechanism, the drug delivery deviceis initiated to: insert a fluid pathway into the user; enable, connect,or open necessary connections between a drug container, a fluid pathway,and a sterile fluid conduit; and force drug fluid stored in the drugcontainer through the fluid pathway and fluid conduit for delivery intoa user. One or more optional safety mechanisms may be utilized, forexample, to prevent premature activation of the drug delivery device.For example, an optional on-body sensor 9224 (shown in FIG. 80C) may beprovided in one embodiment as a safety feature to ensure that the powerand control system, or the activation mechanism 9214, cannot be engagedunless the drug delivery device 9210 is in contact with the body of theuser. In one such embodiment, the on-body sensor 9224 is located on thebottom of lower housing 9212B where it may come in contact with theuser's body. Upon displacement of the on-body sensor 9224, depression ofthe activation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor 9224 is a mechanical safety mechanism,such as for example a mechanical lock out, that prevents triggering ofthe drug delivery device 9210 by the activation mechanism 9214. Inanother embodiment, the on-body sensor may be an electro-mechanicalsensor such as a mechanical lock out that sends a signal to the powerand control system to permit activation. In still other embodiments, theon-body sensor can be electrically based such as, for example, acapacitive- or impedance-based sensor which must detect tissue beforepermitting activation of the power and control system. These conceptsare not mutually exclusive and one or more combinations may be utilizedwithin the breadth of the present disclosure to prevent, for example,premature activation of the drug delivery device. In a preferredembodiment, the drug delivery device 10 utilizes one or more mechanicalon-body sensors. Additional integrated safety mechanisms are describedherein with reference to other components of the novel drug deliverydevices.

XI.A. Power and Control System

The power and control system includes a power source, which provides theenergy for various electrical components within the drug deliverydevice, one or more feedback mechanisms, a microcontroller, a circuitboard, one or more conductive pads, and one or more interconnects. Othercomponents commonly used in such electrical systems may also beincluded, as would be appreciated by one having ordinary skill in theart. The one or more feedback mechanisms may include, for example,audible alarms such as piezo alarms and/or light indicators such aslight emitting diodes (LEDs). The microcontroller may be, for example, amicroprocessor. The power and control system controls several deviceinteractions with the user and interfaces with the drive mechanism92100. In one embodiment, the power and control system interfaces withthe control arm 9240 to identify when the on-body sensor 9224 and/or theactivation mechanism 9214 have been activated. The power and controlsystem may also interface with the status indicator 9216 of the pumphousing 9212, which may be a transmissive or translucent material whichpermits light transfer, to provide visual feedback to the user. Thepower and control system interfaces with the drive mechanism 92100through one or more interconnects to relay status indication, such asactivation, drug delivery, and end-of-dose, to the user. Such statusindication may be presented to the user via auditory tones, such asthrough the audible alarms, and/or via visual indicators, such asthrough the LEDs. In a preferred embodiment, the control interfacesbetween the power and control system and the other components of thedrug delivery device are not engaged or connected until activation bythe user. This is a desirable safety feature that prevents accidentaloperation of the drug delivery device and may additionally maintain theenergy contained in the power source during storage, transportation, andthe like.

The power and control system may be configured to provide a number ofdifferent status indicators to the user. For example, the power andcontrol system may be configured such that after the on-body sensorand/or trigger mechanism have been pressed, the power and control systemprovides a ready-to-start status signal via the status indicator 9216 ifdevice start-up checks provide no errors. After providing theready-to-start status signal and, in an embodiment with the optionalon-body sensor, if the on-body sensor remains in contact with the bodyof the user, the power and control system will power the drive mechanism92100 to begin delivery of the drug treatment through the fluid pathwayconnector 92300 and sterile fluid conduit 9230 (not shown). In apreferred embodiment of the present disclosure, the insertion mechanism92200 and the fluid pathway connector 92300 may be caused to activatedirectly by user operation of the activation mechanism 9214. During thedrug delivery process, the power and control system is configured toprovide a dispensing status signal via the status indicator 9216. Afterthe drug has been administered into the body of the user and after theend of any additional dwell time, to ensure that substantially theentire dose has been delivered to the user, the power and control systemmay provide an okay-to-remove status signal via the status indicator9216. This may be independently verified by the user by viewing thedrive mechanism and drug dose delivery through the window 9218 of thepump housing 9212. Additionally, the power and control system may beconfigured to provide one or more alert signals via the status indicator9216, such as for example alerts indicative of fault or operationfailure situations.

The power and control system may additionally be configured to acceptvarious inputs from the user to dynamically control the drive mechanisms92100 to meet a desired drug delivery rate or profile. For example, thepower and control system may receive inputs, such as from partial orfull activation, depression, and/or release of the activation mechanism9214, to set, initiate, stop, or otherwise adjust the control of thedrive mechanism 92100 via the power and control system to meet thedesired drug delivery rate or profile. Similarly, the power and controlsystem may be configured to receive such inputs to adjust the drug dosevolume; to prime the drive mechanism, fluid pathway connector, and fluidconduit; and/or to start, stop, or pause operation of the drivemechanism 92100. Such inputs may be received by the user directly actingon the drug delivery device 9210, such as by use of the activationmechanism 9214 or a different control interface, or the system 92400 maybe configured to receive such inputs from a remote control device.Additionally or alternatively, such inputs may be pre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism 9214 of the drugdelivery device 9210 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

XI.B. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9210, the fluid pathway connector 92300 isenabled to connect the sterile fluid conduit 30 to the drug container ofthe drive mechanism 92100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 92100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user.

In at least one embodiment of the present disclosure, the piercingmember of the fluid pathway connector is caused to penetrate thepierceable seal of the drug container of the drive mechanism by directaction of the user, such as by depression of the activation mechanism bythe user. For example, the activation mechanism itself may bear on thefluid pathway connector such that displacement of the activationmechanism from its original position also causes displacement of thefluid pathway connector. In one such embodiment, the fluid pathwayconnector may be substantially similar to that described inInternational Patent Application No. PCT/US2012/054861, which isincluded by reference herein in its entirety for all purposes. Accordingto such an embodiment, the connection is enabled by the user depressingthe activation mechanism and, thereby, driving the piercing memberthrough the pierceable seal, because this prevents fluid flow from thedrug container until desired by the user. In such an embodiment, acompressible sterile sleeve may be fixedly attached between the cap ofthe drug container and the connection hub of the fluid pathwayconnector. The piercing member may reside within the sterile sleeveuntil a connection between the fluid connection pathway and the drugcontainer is desired. The sterile sleeve may be sterilized to ensure thesterility of the piercing member and the fluid pathway prior toactivation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Application No.PCT/US2013/030478, for example, which is included by reference herein inits entirety for all purposes. According to such an embodiment, a drugcontainer may have a drug chamber within a barrel between a pierceableseal and a plunger seal. A drug fluid is contained in the drug chamber.Upon activation of the device by the user, a drive mechanism asserts aforce on a plunger seal contained in the drug container. As the plungerseal asserts a force on the drug fluid and any air/gas gap or bubble, acombination of pneumatic and hydraulic pressure builds by compression ofthe air/gas and drug fluid and the force is relayed to the slidingpierceable seal. The sliding pierceable seal is caused to slide towardsthe cap, causing it to be pierced by the piercing member retained withinthe integrated sterile fluid pathway connector. Accordingly, theintegrated sterile fluid pathway connector is connected (i.e., the fluidpathway is opened) by the combination pneumatic/hydraulic force of theair/gas and drug fluid within the drug chamber created by activation ofa drive mechanism. Once the integrated sterile fluid pathway connectoris connected or opened, drug fluid is permitted to flow from the drugcontainer, through the integrated sterile fluid pathway connector,sterile fluid conduit, and insertion mechanism, and into the body of theuser for drug delivery. In at least one embodiment, the fluid flowsthrough only a manifold and a cannula and/or needle of the insertionmechanism, thereby maintaining the sterility of the fluid pathway beforeand during drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 92300 and the sterile fluid conduit 30 are providedhereinafter in later sections in reference to other embodiments.

XI.C. Insertion Mechanism

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure.

In at least one embodiment, the insertion mechanism 92200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 80B and FIG. 80C). The connection of the base to theassembly platform 9220 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9210. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9230 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9227 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane 92254 (shown in FIG. 80C).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. As shown in FIG. 80B, the lockoutpin(s) 92208 may be directly displaced by user depression of theactivation mechanism 9214. As the user disengages any safety mechanisms,such as an optional on-body sensor 9224 (shown in FIG. 80C), theactivation mechanism 9214 may be depressed to initiate the drug deliverydevice. Depression of the activation mechanism 9214 may directly causetranslation or displacement of control arm 40 and directly or indirectlycause displacement of lockout pin(s) 92208 from their initial positionwithin locking windows 92202A of insertion mechanism housing 92202.Displacement of the lockout pin(s) 92208 permits insertion biasingmember to decompress from its initial compressed, energized state. Thisdecompression of the insertion biasing member drives the needle and thecannula into the body of the user. At the end of the insertion stage,the retraction biasing member is permitted to expand in the proximaldirection from its initial energized state. This axial expansion in theproximal direction of the retraction biasing member retracts the needle,while maintaining the cannula in fluid communication with the body ofthe user. Accordingly, the insertion mechanism may be used to insert aneedle and cannula into the user and, subsequently, retract the needlewhile retaining the cannula in position for drug delivery to the body ofthe user.

XI.D. Drive Mechanism

With reference to the embodiments shown in FIGS. 81 and 82, drivemechanism 92100 includes a drive housing 92130, and a drug container9250 having a cap 9252, a pierceable seal (not visible), a barrel 9258,and a plunger seal 9260. A drug chamber 9221, located within the barrel9258 between the pierceable seal and the plunger seal 9260, may containa drug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. The seals described hereinmay be comprised of a number of materials but are, in a preferredembodiment, comprised of one or more elastomers or rubbers. The drivemechanism may further include a connection mount 9254 to guide theinsertion of the piercing member of the fluid pathway connector into thebarrel 9258 of the drug container 9250. The drive mechanism 92100 mayfurther contain one or more drive biasing members, one or more releasemechanisms, and one or more guides, as are described further herein. Thecomponents of the drive mechanism function to force a fluid from thedrug container out through the pierceable seal, or preferably throughthe piercing member of the fluid pathway connector, for delivery throughthe fluid pathway connector, sterile fluid conduit, and insertionmechanism into the body of the user.

In one particular embodiment, the drive mechanism 92100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. The fluid pathway connector may beconnected through the pierceable seal prior to, concurrently with, orafter activation of the drive mechanism to permit fluid flow from thedrug container, through the fluid pathway connector, sterile fluidconduit, and insertion mechanism, and into the body of the user for drugdelivery. In at least one embodiment, the fluid flows through only amanifold and a cannula of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detail herein.

Referring now to the embodiment of the drive mechanism shown in FIG. 81and FIG. 9282, the drive mechanism 92100 includes a drug container 9250having a cap 9252, a pierceable seal (not visible), a barrel 9258, and aplunger seal 9260, and optionally a connection mount 9254. The drugcontainer 9250 is mounted to a distal end of a drive housing 92130.Compressed within the drive housing 92130, between the drug container9250 and the proximal end of the housing 92130, are drive biasingmembers 92122 a and 92122 b and a piston 92110, wherein the drivebiasing members 92122 a, 92122 b are configured to bear upon aninterface surface 92110C of the piston 92110, as described furtherherein. Optionally, a cover sleeve 92140 may be utilized between thedrive biasing members 92122 and the interface surface 92110C of thepiston 92110 to, for example, promote more even distribution of forcefrom the drive biasing member 92122 to the piston 92110, preventbuckling of the drive biasing member 92122, and/or hide biasing members92122 from user view. Interface surface 92110C of piston 92110 is causedto rest substantially adjacent to, or in contact with, a proximal end ofseal 9260. Although the embodiments shown in FIGS. 81 and 82 show aplurality of biasing members it is also contemplated that a singlebiasing member may be used.

As best shown in FIG. 82B, the piston 92110 may be comprised of twocomponents 92110A and 92110B and have an interface surface 92110C tocontact the plunger seal. A tether, ribbon, string, or other retentionstrap (referred to herein as the “tether” 92512) may be connected at oneend to the piston 9210A, 92110B. For example, the tether 92512 may beconnected to the piston 92110A, 92110B by retention between the twocomponents of the piston 92110A, 92110B when assembled. The tether 92512is connected at another end to a winch drum 92520 of a delivery controlmechanism 92500. Through the use of the winch drum 92520 connected toone end of the tether 92512, and the tether 92512 connected at anotherend to the piston 92110A, 92110B, the regulating mechanism 92500functions to control, meter, provide resistance, or otherwise preventfree axial translation of the piston 92110A, 92110B and plunger seal9260 utilized to force a drug substance out of a drug container 9250.Accordingly, the regulating mechanism 92500 and the drive mechanism92100 (collectively referred to herein as the “controlled delivery drivemechanism”) together function to control the rate or profile of drugdelivery to the user.

As shown in FIGS. 81 and 82, in the embodiments of the presentdisclosure, the regulating mechanism 92500 is an escapement regulatingmechanism. The escapement regulating mechanism retards or restrains thedistribution of tether 92512, only allowing it to advance at a regulatedor desired rate. This restricts movement of piston 92110 within barrel9258, hence controlling the movement of plunger seal 9260 and deliveryof the drug contained in chamber 9221. As the plunger seal 9260 advancesin the drug container 9250, the drug substance is dispensed through thesterile pathway connection 92300, conduit 9230, insertion mechanism92200, and into the body of the user for drug delivery. In turn, tensionon tether 92512, caused by the force of biasing member 92122 on piston92110, imparts a torque on winch drum 92520 which is transferred throughgear train 92510 to the escapement regulating mechanism. Optionally, apower spring may be included, coupled to the escapement regulatingmechanism. This may be done in order to impart additional torque to thewinding drum and/or gear train.

In at least one embodiment of the present disclosure, the drivemechanism 92100 utilizes an escapement regulating element 92500. Theregulating element 92500 further includes one or more gears 92512,92514, 92516 of a gear train 92510. One or more of the gears 92512,92514, 92516 may be, for example, compound gears having a small diametergear attached at a shared center point to a large diameter gear. Firstgear 92512 may be rotationally coupled to winch drum 92520, for exampleby a keyed shaft, thereby coupling rotation of gear train 92510 to winchdrum 92520. First compound gear 92512 engages the small diameter gear92514B of compound gear 92514 such that rotational movement of the firstgear 92512 is conveyed by engagement of the gears (such as by engagementof corresponding gear teeth) to the second compound gear 92514. Largegear 92514A of compound gear 92514 engages the small gear 92516B ofsecond compound gear 92516, conveying rotation thereto. Large gear92516A of second compound gear 92516 engages small gear 92562B of escapewheel 92562, thereby coupling rotation of escape wheel 92562 to winchdrum 92520. Rotation of the gear train 92510 may be coupled to winchdrum 92520 thereby controlling the distribution of tether 92512, and therate of movement of plunger seal 9260 within barrel 9258 to force afluid from drug chamber 9221. The rotational movement of the winch drum92520, and thus the axial translation of the piston 92110 and plungerseal 9260, are metered, restrained, or otherwise prevented from freeaxial translation by other components of the escapement regulatingelement 92500, as described herein.

The escape wheel 92562 is a compound gear having escape teeth around thecircumference of a large diameter escape gear 92562A and a smalldiameter gear 92562B (not visible) configured to engage the gear train92510 and meter, restrain, or otherwise prevent free rotational movementthereof. The escapement regulating element 500 further includes a lever92564. The lever 92564 has pins 92564A,B and prong 92564C. Prong 92564Cmovably engages a post 92566A and is configured to removably engage animpulse pin 92566B of a balance wheel 92566. The balance wheel 92566engages and functions as an oscillator around a pivot point 92564D incombination with a hair spring 92568. The gear train 92510, escape wheel92562, balance wheel 92566, hair spring 92568, and lever 92564 may bemounted on and able to freely rotate or move on a first plate 92504and/or a second plate 92506. The first plate 92504 and second plate92506 may utilize one or more spacer columns to maintain the desiredspacing between components and one or more pivot pins upon which thecomponents may be mounted and freely rotated. An electromechanicalactuator 92570 may be provided in addition to or in lieu of the hairspring 92568. Electromechanical actuator 92570 may be configured tocontrol and/or adjust the rotation and/or oscillation of balance wheel92566 as will be discussed further hereinafter.

The function of the escape wheel 92562, balance wheel 92566, hair spring92568, and lever 92564 components of the escapement regulating element92500 are explained with reference to FIG. 81B and FIGS. 83A-83H. Theescape wheel 92562 and lever 92564 may initially be in an activationposition, as shown in FIG. 83A. The escape wheel 562 and lever 92564generally function to perform two steps, termed the locking action andthe impulse action. These two actions are illustrated in FIG. 83B andFIG. 83C, respectively, and in which the gear train 510 is applying aclockwise torque on the escape wheel 92562. The clockwise torque maycome as a result of biasing members 92122 applying a force to piston92110 which in turn applies a tension to tether 92512. The tension oftether 92512 imparts a torque on winding drum 92520 which is transmittedthrough gear train 92510 to escape wheel 92562. Optionally, a powerspring may additionally be used to impart torque to gear train 92510. Inthe locking action, one of two lever pins 92564A,B blocks escape wheel92562 rotation on the radial face of a tooth on the escape gear 92562A.This locks the gear train 92510 between impulse actions. In the impulseaction, a lever pin 92564A,B slides up to this tooth face due to actionof the balance wheel 92566 on the lever 92564. The escape wheel becomesunlocked and does mechanical work on the lever pin 92564A, B via asliding action, which in turn imparts kinetic energy to the balancewheel 92566. The lever 92564 pivots upon a pivot point 92564D until theopposite pin 92564A,B engages with an escape wheel tooth on the escapegear 92562A, and the locked state is re-entered after a half toothadvance of the escape wheel 92562. The transition from locking action toimpulse action is triggered by the balance wheel 92566, which functionsas an oscillator in combination with the hair spring 92568 and/orelectromechanical actuator 92570. It cycles at a natural frequency thatserves as the rate control. Alternatively, the rate can be controlledand/or varied by the electromechanical actuator 92570. The balance wheel92566 contains an impulse pin 92566B which interacts with the lever92564 at prong 92564C. For the impulse phase depicted in FIG. 83C, aclockwise moment on the lever 92564 exerts a counterclockwise moment onthe balance wheel 92566, adding to its kinetic energy. The balance wheel92566 rotates until its kinetic energy is absorbed by the hair spring92568 or until it is caused to stop by electromechanical actuator 92570.It stops, reverses, and reengages the impulse pin 92566B with the lever92564. A complete cycle is shown in the transition between FIGS.83D-83H. For example, a motor (e.g., a DC motor, AC motor, or steppermotor) or a solenoid (e.g., linear solenoid, rotary solenoid) may beused to rotate the balance wheel. This electromechanical actuator may beused in addition to the hair spring or in place of the hair spring. Theelectromechanical actuator may be controlled by the power and controlsystem. By providing an electromechanical actuator the rate of drugdelivery may be adjusted and/or controlled. In one embodiment,electromechanical actuator 92570 is a rotary solenoid. Upon receipt ofan input signal from the power and control system the core of the rotarysolenoid may rotate. This rotation may be imparted to balancing wheel92566 by, for example, a keyed shaft. The rotary solenoid may later,upon either removal of the input signal or the receipt of a second inputsignal, rotate the balancing wheel back in the opposite direction or,alternatively, a hair spring may be used to return the balancing wheelin the opposite direction. This action could similarly be performed by alinear solenoid using an appropriate linkage to convert the linearmotion of the solenoid core to rotational motion of the balancing wheel.A motor may also be configured to perform similarly.

To unlock the escapement regulating mechanism 92500, the balance wheel92566 must have enough kinetic energy to drag the lever pin 92564A,B upthe face of the tooth of the escape gear 92562A of the escape wheel92562. If the impulse action adds less energy than is lost to friction,the balance wheel 92566 will rotate less and less and finally stall,locking the escapement regulating mechanism 92500. If the escapementstops in this way under load, it will not restart easily. To beself-starting, the hair spring 92568 must align the lever 92564 alongthe axis connecting the pivot of the escape wheel 92562 and the pivot ofthe balance wheel 92566, as shown in FIG. 83A. The lever pins 92564A,Bwill be positioned so that a bevel tooth face can immediately start animpulse action upon application of a drive torque. This alignment canoccur only with the escapement regulating mechanism 92500 in an unloadedstate. The tension on the tether provided by the force of the biasingmember 92122 on the piston 92110 must be isolated from the escapementregulating mechanism 500 until the start of delivery. This may be doneby, for example, providing a lock-out feature which, in a firstconfiguration, prevents motion of piston 92110. After transformation toa second configuration, the lock-out feature does not prevent motion ofpiston 92110 and thereafter the tension on tether 92512 acts to create atorque on winding drum 92520. Alternatively, escapement regulatingmechanism 92500 may be initiated by a user imparting a force on anactivation mechanism and, directly or indirectly through a power andcontrol system, applying a drive torque to start the initial impulseaction. Once the escapement regulating mechanism 92500 is initiated, itcan be effectively utilized to meter, restrain, or otherwise preventfree rotational movement of the gear train 92510, winding drum 92520 andpiston 92110, and, thus, plunger seal 9260. In a particular embodiment,the escape wheel 92562 is a compound gear having escape teeth around thecircumference of a large diameter escape gear 92562A and a smalldiameter gear 92562B (not visible). The small diameter gear 92562B ofthe escape wheel 92562 engages the drive train 92510, which engages withwinding drum 92520 through rotation shaft 92518. This novelconfiguration directly permits the escape wheel 92562 to regulate therotation of the drive train 92510 and winding drum 92520, which thenefficiently regulates the tether 92512 and the piston 92110.

Notably, the regulating mechanisms 92500 of the present disclosure donot drive the delivery of fluid substances from the drug chamber 9221.The delivery of fluid substances from the drug chamber 9221 is caused bythe expansion of the biasing member 92122 from its initial energizedstate acting upon the piston 92110A, 92110B and plunger seal 9260. Theregulating mechanisms 92500 instead function to provide resistance tothe free motion of the piston 92110A, 92110B and plunger seal 9260 asthey are pushed by the expansion of the biasing member 92122 from itsinitial energized state. The regulating mechanism 92500 does not drivethe delivery but only controls the delivery motion. The tether limits orotherwise restrains the motion of the piston 92110 and plunger seal9260, but does not apply the force for the delivery. According to apreferred embodiment, the controlled delivery drive mechanisms and drugdelivery devices of the present disclosure include an escapementregulating mechanism indirectly or directly connected to a tethermetering the axial translation of the piston 92110A, 92110B and plungerseal 9260, which are being driven to axially translate by the biasingmember 92122. The rate of drug delivery as controlled by the regulatingmechanism may be determined by: selection of the gear ratio of geartrain 92510; selection of the spring rate of hair spring 92568;selection of the diameter of winding drum 92520; using electromechanicalactuator 92570 to control the rate of oscillation and/or rotation ofbalance wheel 92566; or any other method known to one skilled in theart. By using electromechanical actuator 92570 to control theoscillation and/or rotation of balance wheel 92566 it may be possible toconfigure a drug delivery device to provide a variable dose rate (i.e.,the rate of drug delivery is varied during a treatment).

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether 92512 by the winch drum 92520 and thereby permit axialtranslation of the piston 92110 by the biasing member 92122 to translatea plunger seal 9260 within a barrel 9258. The one or more inputs may beprovided by the actuation of the activation mechanism 9214, a controlinterface, and/or a remote control mechanism. The power and controlsystem may be configured to receive one or more inputs to adjust therestraint provided by the tether 59212 and winch drum 92520 on the freeaxial translation of the piston 92110 upon which the biasing member92122 bears upon to meet a desired drug delivery rate or profile, tochange the dose volume for delivery to the user, and/or to otherwisestart, stop, or pause operation of the drive mechanism.

The components of the drive mechanism 92100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9260 of the drug container 9250. Optionally, the drive mechanism92100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9260 to, for example,ensure that substantially the entire drug dose has been delivered to theuser. For example, the plunger seal 9260, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user.

The tether 92512 may have one or more status triggers, such aselectrical contacts, optical markings, or electromechanical pins orrecesses, which are capable of contacting or being recognized by astatus reader. In at least one embodiment, an end-of-dose statusindication may be provided to the user once the status reader contactsor recognizes the final status trigger positioned on the tether 92512that would contact the status reader at the end of axial travel of thepiston 92110A, 92110B and plunger 60 within the barrel 9258 of the drugcontainer 9250. The status reader may be, for example, an electricalswitch reader to contact the corresponding electrical contacts, anoptical reader to recognize the corresponding optical markings, or amechanical or electromechanical reader configured to contactcorresponding pins, holes, or similar aspects on the tether. The statustriggers may be positioned along the tether 92512 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asthe drug delivery device is activated and drug delivery is begun byrelease of the biasing member 92122 and the resulting force applied tothe piston 92110A, 92110B and plunger seal 9260, the rate or profile ofdrug delivery to the user is controlled by the escapement regulatingmechanism, gear assembly, and winch drum 92520 releasing the tether92512 and permitting expansion of the biasing member 92122 and axialtranslation of the piston 92110A, 92110B and plunger seal 9260. As thisoccurs, the status triggers of the tether 92512 are contacted orrecognized by the status reader and the status of the drive mechanismbefore, during, and after operation can be relayed to the power andcontrol system to provide feedback to the user. Depending on the numberof status triggers located on the tether 92512, the frequency of theincremental status indication may be varied as desired. As describedabove, a range of status readers may be utilized depending on the statustriggers utilized by the system.

In a preferred embodiment, the status reader may apply a tensioningforce to the tether 92512. When the system reaches end-of-dose, thetether 92512 goes slack and the status reader 92544 is permitted torotate about a fulcrum. This rotation may operate an electrical orelectromechanical switch, for example a switch, signaling slack in thetether 92512 to the power and control system. Additionally, a gear ofgear train 92510 may act as an encoder along with a sensor. Thesensor/encoder combination is used to provide feedback of gear trainrotation, which in turn can be calibrated to the position of piston92110 when there is no slack in the tether 92512. Together, the statusreader and sensor/encoder may provide positional feedback, end-of-dosesignal, and error indication, such as an occlusion, by observing slackin the tether 92512 prior to reaching the expected number of motorrotations as counted by the sensor/encoder.

Further aspects of the novel drive mechanism will be described withreference to FIGS. 84A-84B and 85A-85C. FIG. 84A shows an isometric viewof the drive mechanism, according to at least a first embodiment, duringits initial locked stage. A fluid, such as a drug fluid, may becontained within barrel 9258, in a drug chamber 9221 between plungerseal 9260 and a pierceable seal (not visible), for delivery to a user.The pierceable seal is adjacent or retained at least partially withincap 9252. Upon activation by the user, a fluid pathway connector may beconnected to the drug container through the pierceable seal 9256. Asdescribed above, this fluid connection may be facilitated by a piercingmember of the fluid pathway connector which pierces the pierceable sealand completes the fluid pathway from the drug container, through thefluid pathway connector, the fluid conduit, the insertion mechanism, andthe cannula for delivery of the drug fluid to the body of the user.Initially, one or more locking mechanisms (not shown) may retain thebiasing member 92122 in an initial energized position within piston92110A, 92110B. Directly or indirectly upon activation of the device bythe user, the locking mechanism may be removed to permit operation ofthe drive mechanism. Removal of the locking mechanism may permit thebiasing member to impart a force to piston 92110 and therefore to tether92512. This force on tether 92512 imparts a torque on winding drum 92520which causes the gear train and escapement regulating mechanism to beginmotion. As shown in FIG. 85A, the piston 92110 and biasing member 92122are both initially in a compressed, energized state behind the plungerseal 9260. The biasing member 92122 may be maintained in this stateuntil activation of the device between internal features of drivehousing 92130 and interface surface 92110C of piston 92110A, 92110B. Asthe locking mechanism is removed or displaced, biasing member 92122 ispermitted to expand (i.e., decompress) axially in the distal direction(i.e., in the direction of the hatched arrow). Such expansion causes thebiasing member 92122 to act upon and distally translate interfacesurface 92110C and piston 92110, thereby distally translating plungerseal 9260 to push drug fluid out of the drug chamber 9221 of barrel9258.

As shown in FIG. 85B, such distal translation of the piston 92110A,92110B and plunger seal 9260 continues to force fluid flow out frombarrel 9258 through the pierceable seal 9256. In at least oneembodiment, an end-of-dose status indication may be provided to the useronce the status reader contacts or recognizes a status triggerpositioned on the tether 92512 to substantially correspond with the endof axial travel of the piston 92110A, 92110B and plunger seal 9260within the barrel 9258 of the drug container 9250. The status triggersare positioned along the tether 92512 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the user. In at least one embodiment,the status reader is an optical status reader configured to recognizethe corresponding optical status triggers on the tether. As would beunderstood by an ordinarily skilled artisan, such optical statustriggers may be markings which are recognizable by the optical statusreader. In another embodiment, the status reader is a mechanical orelectromechanical reader configured to physically contact correspondingpins, holes, or similar aspects on the tether. Electrical contacts couldsimilarly be utilized on the tether as status indicators which contactor are otherwise recognized by the corresponding electrical statusreader. The status triggers may be positioned along the tether 92512 tobe read or recognized at positions which correspond with the beginningand end of drug delivery, as well as at desired increments during drugdelivery. As shown, tether 92512 passes substantially axially throughthe drive mechanism housing 130, the biasing member 92122, and connectsto the piston 92110 A, 92110B to restrict the axial translation of thepiston 92110A, 92110B and the plunger seal 9260 that resides adjacentthereto.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement ofwinding drum 92520 and, thus, axial translation of the components of thecontrolled delivery drive mechanism 92100. Accordingly, the escapementregulating mechanism 92500 only controls the motion of the drivemechanism, but does not apply the force for the drug delivery. One ormore additional biasing members 92122, such as compression springs, maybe utilized to drive or assist the driving of the piston 92110. Forexample, a compression spring may be utilized within the drive housing92130 for this purpose. The escapement regulating mechanism 92500 onlycontrols, meters, or regulates such action. A mechanical timing system,such as the escapement regulating mechanism described herein, may beutilized to allow the piston 92110 and plunger seal 9260 to translateaxially a controlled distance, or a controlled volume, and may beutilized to meet a desired delivery rate or profile. The timing systemcan be controlled by quartz timing instead of mechanical timing, aswould be appreciated by one having ordinary skill in the art. For quartztiming, a battery provides power to a microchip and circuit. The quartzcrystal oscillates at a precise frequency. Alternate electrical timingmechanisms such as, for example, RC timing mechanisms, may also be used,including clock functions commonly found in microprocessors. Dependingon the period that the delivery is planned to occur over, the microchipdrives a motor based on a number of quartz crystal oscillations or othertiming signals. The motor releases motion of a drive train to controlthe axial translation of a plunger in a similar manner as describedherein for the mechanical timing system.

The delivery control mechanisms 92500 of the present disclosure do notdrive the delivery of fluid substances from the drug chamber 9221. Thedelivery of fluid substances from the drug chamber 9221 is caused by theexpansion of the biasing member 92122 from its initial energized stateacting upon the piston 92110A, 92110B and plunger seal 9260. Thedelivery control mechanisms 92500 instead function to provide resistanceto the free motion of the piston 92110A, 92110B and plunger seal 9260 asthey are pushed by the expansion of the biasing member 92122 from itsinitial energized state. As the delivery control mechanisms 92500release the tether 92512, the biasing member 92122 is permitted tocontinue its expansion from its energized state and drive the piston92110A, 92110B and plunger seal 9260 until the plunger seal 9260 hassubstantially contacted the pierceable seal 9256. This is visible in thecross-sectional view provided in FIG. 85C. At this point, substantiallyall of the drug substance has been pushed out of the drug chamber 9221through the fluid pathway connector 92300 for drug delivery to the user.A status trigger may be configured along the tether 92512 to correspondwith this position of the piston 92110A, 92110B, such that, as thepiston 92110A, 92110B reaches its end of axial travel, a status triggeris read or recognized by the status reader to provide true end-of-doseindication to the user. As stated above, the status triggers may bepositioned along the tether 92512 to be read or recognized at positionswhich correspond with the beginning and end of drug delivery, as well asat desired increments during drug delivery. The controlled deliverydrive mechanisms and/or drug delivery devices of the present disclosuremay additionally enable a compliance push to ensure that substantiallyall of the drug substance has been pushed out of the drug chamber 9221.The plunger seal 9260, itself, may have some compressibility permittinga compliance push of drug fluid from the drug container. For example,when a pop-out plunger seal is employed, i.e., a plunger seal that isdeformable from an initial state, the plunger seal may be caused todeform or “pop-out” to provide a compliance push of drug fluid from thedrug container, as shown in FIG. 85C. Additionally or alternatively, anelectromechanical status switch and interconnect assembly may beutilized to contact, connect, or otherwise enable a transmission to thepower and control system to signal end-of-dose to the user. For example,the status switch may be located distal to the pierceable seal 9256 andthe interconnect located proximal to the plunger seal 9260 such that,upon substantially complete axial translation (and optional compliancepush) of the plunger seal 9260 within the barrel 9258, the status switchand interconnect coordinate to enable a transmission to the power andcontrol system to signal end-of-dose to the user. This configurationfurther enables true end-of-dose indication to the user.

In at least one embodiment, incremental status indication may beprovided to the user by reading or recognizing the rotational movementof one or more gears of gear train 92510. As the gear train 92510rotates, a status reader may read or recognize one or more correspondingstatus triggers on one of the gears in the gear train to provideincremental status indication before, during, and after operation of thevariable rate controlled delivery drive mechanism. A number of statusreaders may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism may utilize a mechanicalstatus reader which is physically contacted by gear teeth of one of thegears of the gear train. As the status reader is contacted by the statustrigger(s), which in this exemplary embodiment may be the gear teeth ofone of the gears (or holes, pins, ridges, markings, electrical contacts,or the like, upon the gear), the status reader measures the rotationalposition of the gear and transmits a signal to the power and controlsystem for status indication to the user. Additionally or alternatively,the drive mechanism may utilize an optical status reader. The opticalstatus reader may be, for example, a light beam that is capable ofrecognizing a motion and transmitting a signal to the power and controlsystem. For example, the drive mechanism may utilize an optical statusreader that is configured to recognize motion of the gear teeth of oneof the gears in the gear train (or holes, pins, ridges, markings,electrical contacts, or the like, upon the gear). Similarly, the statusreader may be an electrical switch configured to recognize electricalcontacts on the gear. In any of these embodiments, the sensor may beutilized to then relay a signal to the power and control system toprovide feedback to the user.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to the user.While the drive mechanisms of the present disclosure are described withreference to the gear train and escapement regulating mechanism shown inthe figures, a range of configurations may be acceptable and capable ofbeing employed within the embodiments of the present disclosure, aswould readily be appreciated by an ordinarily skilled artisan.Accordingly, the embodiments of the present disclosure are not limitedto the specific gear train and escapement regulating mechanism describedherein, which is provided as an exemplary embodiment of such mechanismsfor employment within the controlled delivery drive mechanisms and drugdelivery pumps.

Assembly and/or manufacturing of controlled delivery drive mechanism100, drug delivery pump 10, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9250 may first be assembledand filled with a fluid for delivery to the user. The drug container9250 includes a cap 9252, a pierceable seal 9256, a barrel 9258, and aplunger seal 9260. The pierceable seal 9256 may be fixedly engagedbetween the cap 9252 and the barrel 9258, at a distal end of the barrel9258. The barrel 9258 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9260 from theproximal end of the barrel 9258. An optional connection mount 9254 maybe mounted to a distal end of the pierceable seal 9256. The connectionmount 9254 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9258 of the drug container 9250. Thedrug container 9250 may then be mounted to a distal end of drive housing92130.

One or more drive biasing members 92122 may be inserted into a distalend of the drive housing 92130. Optionally, a cover sleeve 92140 may beinserted into a distal end of the drive housing 92130 to substantiallycover biasing member 92122. A piston may be inserted into the distal endof the drive housing 92130 such that it resides at least partiallywithin an axial pass-through of the biasing member 92122 and the biasingmember 92122 is permitted to contact a piston interface surface 92110Cof piston 92110A, 92110B at the distal end of the biasing member 92122.An optional cover sleeve 92140 may be utilized to enclose the biasingmember 92122 and contact the piston interface surface 92110C of piston92110A, 92110B. The piston 92110A, 92110B and drive biasing member92122, and optional cover sleeve 92140, may be compressed into drivehousing 92130. Such assembly positions the drive biasing member 92122 inan initial compressed, energized state and preferably places a pistoninterface surface 110C in contact with the proximal surface of theplunger seal 9260 within the proximal end of barrel 58. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 92130 prior to attachment or mounting of the drug container9250. The tether 92512 is pre-connected to the proximal end of thepiston 92110A, 92110B and passed through the axial aperture of thebiasing member 92122 and drive mechanism 92130, and then wound throughthe interior of the drug delivery device with the other end of thetether 92512 wrapped around the winch drum 92520 of the regulatingmechanism 92500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 80B.

Certain optional standard components or variations of drive mechanism92100 or drug delivery device 9210 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9218, as shown inFIG. 80A, to enable the user to view the operation of the drug deliverydevice 9210 or verify that drug dose has completed. Similarly, the drugdelivery device 9210 may contain an adhesive patch 9226 and a patchliner 9228 on the bottom surface of the housing 9212. The adhesive patch9226 may be utilized to adhere the drug delivery device 9210 to the bodyof the user for delivery of the drug dose. As would be readilyunderstood by one having ordinary skill in the art, the adhesive patch9226 may have an adhesive surface for adhesion of the drug deliverydevice to the body of the user. The adhesive surface of the adhesivepatch 9226 may initially be covered by a non-adhesive patch liner 9228,which is removed from the adhesive patch 9226 prior to placement of thedrug delivery device 9210 in contact with the body of the user. Removalof the patch liner 9228 may further remove the sealing membrane 92254 ofthe insertion mechanism 92200, opening the insertion mechanism to thebody of the user for drug delivery (as shown in FIG. 80C).

Similarly, one or more of the components of controlled delivery drivemechanism 92100 and drug delivery device 9210 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9210 is shown as two separate components upper housing9212A and lower housing 9212B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The novel controlleddelivery drive mechanisms of the present disclosure may be directly orindirectly activated by the user. Furthermore, the novel configurationsof the controlled delivery drive mechanism and drug delivery devices ofthe present disclosure maintain the sterility of the fluid pathwayduring storage, transportation, and through operation of the device.Because the path that the drug fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe drug container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent disclosure do not require terminal sterilization upon completionof assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connector, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a user, wherein aregulating mechanism acting to restrain the distribution of a tether isutilized to meter the free axial translation of the piston. The methodof operation of the insertion mechanism and the drug delivery device maybe better appreciated with reference to FIGS. 84A-84B and FIGS. 85A-85C,as described above.

XII. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 69A-73D, and 80A-85C may be configured to incorporatethe embodiments of the drive mechanism described below in connectionwith FIGS. 86A-91. The embodiments of the drive mechanism describedbelow in connection with FIGS. 86A-91 may be used to replace, in itsentirety or partially, the above-described drive mechanism 100, 6100,8100, 9010, or 9210, or any other drive mechanism described herein,where appropriate.

The present disclosure provides drive mechanisms for the controlleddelivery of drug substances, drug delivery pumps with controlleddelivery drive mechanisms, the methods of operating such devices, andthe methods of assembling such devices. Notably, the drive mechanisms ofthe present disclosure control the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer. The novel embodiments of the present disclosure thus arecapable of delivering drug substances at variable rates. The controlleddelivery drive mechanisms of the present disclosure may bepre-configurable or dynamically configurable, such as by control by thepower and control system, to meet desired delivery rates or profiles, asexplained in detail below. Additionally, the drive mechanisms of thepresent disclosure provide integrated status indication features whichprovide feedback to the user before, during, and after drug delivery.For example, the user may be provided an initial feedback to identifythat the system is operational and ready for drug delivery. Uponactivation, the system may then provide one or more drug delivery statusindications to the user. At completion of drug delivery, the drivemechanism and drug delivery device may provide an end-of-doseindication. Because the end-of-dose indication is related to thephysical end of axial translation of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the novel devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a controlleddelivery drive mechanism which includes a drive housing, a piston, and abiasing member, wherein the biasing member is initially retained in anenergized state and is configured to bear upon an interface surface ofthe piston. The piston is configured to translate substantially axiallywithin a drug container having a plunger seal and a barrel. A tether isconnected at one end to the piston and at another end to a winch drum ofa delivery control mechanism, wherein the tether restrains the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The drug container may contain a drug fluid within a drug chamberfor delivery to a user. Optionally, a cover sleeve may be utilizedbetween the biasing member and the interface surface of the piston tohide the interior components of the barrel (namely, the piston and thebiasing member) from view during operation of the drive mechanism. Thetether is configured to be released from a winch drum of the deliverycontrol mechanism to meter the free expansion of the biasing member fromits initial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In another embodiment, the drive mechanism further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum upon which the tether may be releasably wound, a worm gearengageably connected to the winch gear, a compound gear engageablyconnected to the worm gear, and a motor having a pinion engageablyconnected to the compound gear, wherein the motor is configured to drivethe gear assembly to release the tether from the winch drum to meter thefree expansion of the biasing member from its initial energized stateand the free axial translation of the piston upon which the biasingmember bears upon. The metering of the tether by the motor controls therate or profile of drug delivery to a user. The piston may be one ormore parts and connects to a distal end of the tether.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug having a housing and anassembly platform, upon which an activation mechanism, an insertionmechanism, a fluid pathway connector, a power and control system, and acontrolled delivery drive mechanism may be mounted, said drive mechanismhaving a drive housing, a piston, and a biasing member, wherein thebiasing member is initially retained in an energized state and isconfigured to bear upon an interface surface of the piston. The pistonis configured to translate substantially axially within a drug containerhaving a plunger seal and a barrel. A tether is connected at one end tothe piston and at another end to a winch drum of a delivery controlmechanism, wherein the tether restrains the free expansion of thebiasing member from its initial energized state and the free axialtranslation of the piston upon which the biasing member bears upon. Thedrug container may contain a drug fluid within a drug chamber fordelivery to a user. Optionally, a cover sleeve may be utilized betweenthe biasing member and the interface surface of the piston to hide theinterior components of the barrel (namely, the piston and the biasingmember) from view during operation of the drive mechanism. The tether isconfigured to be released from a winch drum of the delivery controlmechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum upon which the tether may be releasably wound, a worm gearengageably connected to the winch gear, a compound gear engageablyconnected to the worm gear, and a motor having a pinion engageablyconnected to the compound gear, wherein the motor is configured to drivethe gear assembly to release the tether from the winch drum to meter thefree expansion of the biasing member from its initial energized stateand the free axial translation of the piston upon which the biasingmember bears upon. The metering of the tether by the motor controls therate or profile of drug delivery to a user. The piston may be one ormore parts and connects to a distal end of the tether.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch drum and thereby permit axial translation ofthe piston by the biasing member to translate a plunger seal within abarrel. The one or more inputs may be provided by the actuation of theactivation mechanism, a control interface, and/or a remote controlmechanism. The power and control system may be configured to receive oneor more inputs to adjust the restrain provided by the tether and winchdrum on the free axial translation of the piston upon which the biasingmember bears upon to meet a desired drug delivery rate or profile, tochange the dose volume for delivery to the user, and/or to otherwisestart, stop, or pause operation of the drive mechanism.

The novel embodiments of the present disclosure provide drive mechanismswhich are capable of metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thereby, controlling therate of delivery of drug substances. The novel control delivery drivemechanisms are additionally capable of providing the incremental statusof the drug delivery before, during, and after operation of the device.Throughout this specification, unless otherwise indicated, “comprise,”“comprises,” and “comprising,” or related terms such as “includes” or“consists of,” are used inclusively rather than exclusively, so that astated integer or group of integers may include one or more othernon-stated integers or groups of integers. As will be described furtherbelow, the embodiments of the present disclosure may include one or moreadditional components which may be considered standard components in theindustry of medical devices. For example, the embodiments may includeone or more batteries utilized to power the motor, drive mechanisms, anddrug delivery devices of the present disclosure. The components, and theembodiments containing such components, are within the contemplation ofthe present disclosure and are to be understood as falling within thebreadth and scope of the present disclosure.

The present disclosure provides drive mechanisms for the controlleddelivery of drug substances and drug delivery pumps which incorporatesuch controlled delivery drive mechanisms. The drive mechanisms of thepresent disclosure control the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer and, thus, are capable of delivering drug substances atvariable rates and/or delivery profiles. Additionally, the drivemechanisms of the present disclosure provide integrated statusindication features which provide feedback to the user before, during,and after drug delivery. For example, the user may be provided aninitial feedback to identify that the system is operational and readyfor drug delivery. Upon activation, the system may then provide one ormore drug delivery status indications to the user. At completion of drugdelivery, the drive mechanism and drug delivery device may provide anend-of-dose indication.

The novel devices of the present disclosure provide drive mechanismswith integrated status indication and drug delivery pumps whichincorporate such drive mechanisms. Such devices are safe and easy touse, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. The novel devices of the presentdisclosure provide these desirable features without any of the problemsassociated with known prior art devices. Certain non-limitingembodiments of the novel drug delivery pumps, drive mechanisms, andtheir respective components are described further herein with referenceto the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.86A-86C show an exemplary drug delivery device according to at least oneembodiment of the present disclosure. The drug delivery device may beutilized to administer delivery of a drug treatment into a body of auser. As shown in FIGS. 86A-86C, the drug delivery device 9310 includesa pump housing 9312. Pump housing 9312 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug delivery device. Forexample, drug delivery device 9310 includes a pump housing 9312 whichincludes an upper housing 9312A and a lower housing 9312B. The drugdelivery device may further include an activation mechanism 9314, astatus indicator 9316, and a window 9318. Window 9318 may be anytranslucent or transmissive surface through which the operation of thedrug delivery device may be viewed. As shown in FIG. 86B, drug deliverydevice further includes assembly platform 9320, sterile fluid conduit9330, drive mechanism 93100 having drug container 9350, insertionmechanism 93200, fluid pathway connector 93300, and power and controlsystem 93400. One or more of the components of such drug deliverydevices may be modular in that they may be, for example, pre-assembledas separate components and configured into position onto the assemblyplatform 9320 of the drug delivery device 9310 during manufacturing.

The pump housing 9312 contains all of the device components and providesa means of removably attaching the device 9310 to the skin of the user.The pump housing 9312 also provides protection to the interiorcomponents of the device 9310 against environmental influences. The pumphousing 9312 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9312 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9312 may include certaincomponents, such as status indicator 9316 and window 9318, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9310 provides anactivation mechanism 9314 that is displaced by the user to trigger thestart command to the power and control system 93400. In a preferredembodiment, the activation mechanism is a start button 9314 that islocated through the pump housing 9312, such as through an aperturebetween upper housing 9312A and lower housing 9312B, and which contactsa control arm 9340 of the power and control system 93400. In at leastone embodiment, the start button 9314 may be a push button, and in otherembodiments, may be an on/off switch, a toggle, or any similaractivation feature known in the art. The pump housing 9312 also providesa status indicator 9316 and a window 9318. In other embodiments, one ormore of the activation mechanism 9314, the status indicator 9316, thewindow 9318, and combinations thereof may be provided on the upperhousing 9312A or the lower housing 9312B such as, for example, on a sidevisible to the user when the drug delivery device 9310 is placed on thebody of the user. Housing 9312 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device is configured such that, upon activation by a userby depression of the activation mechanism, the drug delivery device isinitiated to: insert a fluid pathway into the user; enable, connect, oropen necessary connections between a drug container, a fluid pathway,and a sterile fluid conduit; and force drug fluid stored in the drugcontainer through the fluid pathway and fluid conduit for delivery intoa user. One or more optional safety mechanisms may be utilized, forexample, to prevent premature activation of the drug delivery device.For example, an optional on-body sensor 9324 (shown in FIG. 86C) may beprovided in one embodiment as a safety feature to ensure that the powerand control system 93400, or the activation mechanism, cannot be engagedunless the drug delivery device 9310 is in contact with the body of theuser. In one such embodiment, the on-body sensor 9324 is located on thebottom of lower housing 9312B where it may come in contact with theuser's body. Upon displacement of the on-body sensor 9324, depression ofthe activation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor 9324 is a mechanical safety mechanism,such as for example a mechanical lock out, that prevents triggering ofthe drug delivery device 9310 by the activation mechanism 9314. Inanother embodiment, the on-body sensor may be an electro-mechanicalsensor such as a mechanical lock out that sends a signal to the powerand control system 93400 to permit activation. In still otherembodiments, the on-body sensor can be electrically based such as, forexample, a capacitive- or impedance-based sensor which must detecttissue before permitting activation of the power and control system93400. These concepts are not mutually exclusive and one or morecombinations may be utilized within the breadth of the presentdisclosure to prevent, for example, premature activation of the drugdelivery device. In a preferred embodiment, the drug delivery device9310 utilizes one or more mechanical on-body sensors. Additionalintegrated safety mechanisms are described herein with reference toother components of the novel drug delivery devices.

XII.A. Power and Control System

The power and control system 93400 includes a power source, whichprovides the energy for various electrical components within the drugdelivery device, one or more feedback mechanisms, a microcontroller, acircuit board, one or more conductive pads, and one or moreinterconnects. Other components commonly used in such electrical systemsmay also be included, as would be appreciated by one having ordinaryskill in the art. The one or more feedback mechanisms may include, forexample, audible alarms such as piezo alarms and/or light indicatorssuch as light emitting diodes (LEDs). The microcontroller may be, forexample, a microprocessor. The power and control system 93400 controlsseveral device interactions with the user and interfaces with the drivemechanism 93100. In one embodiment, the power and control system 93400interfaces with the control arm 9340 to identify when the on-body sensor9324 and/or the activation mechanism 9314 have been activated. The powerand control system 93400 may also interface with the status indicator9316 of the pump housing 9312, which may be a transmissive ortranslucent material which permits light transfer, to provide visualfeedback to the user. The power and control system 93400 interfaces withthe drive mechanism 93100 through one or more interconnects to relaystatus indication, such as activation, drug delivery, and end-of-dose,to the user. Such status indication may be presented to the user viaauditory tones, such as through the audible alarms, and/or via visualindicators, such as through the LEDs. In a preferred embodiment, thecontrol interfaces between the power and control system and the othercomponents of the drug delivery device are not engaged or connecteduntil activation by the user. This is a desirable safety feature thatprevents accidental operation of the drug delivery device and mayadditionally maintain the energy contained in the power source duringstorage, transportation, and the like.

The power and control system 93400 may be configured to provide a numberof different status indicators to the user. For example, the power andcontrol system 93400 may be configured such that after the on-bodysensor and/or trigger mechanism have been pressed, the power and controlsystem 93400 provides a ready-to-start status signal via the statusindicator 9316 if device start-up checks provide no errors. Afterproviding the ready-to-start status signal and, in an embodiment withthe optional on-body sensor, if the on-body sensor remains in contactwith the body of the user, the power and control system 93400 will powerthe drive mechanism 93100 to begin delivery of the drug treatmentthrough the fluid pathway connector 93300 and sterile fluid conduit9330. In a preferred embodiment of the present disclosure, the insertionmechanism 93200 and the fluid pathway connector 93300 may be caused toactivate directly by user operation of the activation mechanism 9314.During the drug delivery process, the power and control system 93400 isconfigured to provide a dispensing status signal via the statusindicator 9316. After the drug has been administered into the body ofthe user and after the end of any additional dwell time, to ensure thatsubstantially the entire dose has been delivered to the user, the powerand control system 93400 may provide an okay-to-remove status signal viathe status indicator 9316. This may be independently verified by theuser by viewing the drive mechanism and drug dose delivery through thewindow 9318 of the pump housing 9312. Additionally, the power andcontrol system 93400 may be configured to provide one or more alertsignals via the status indicator 9316, such as for example alertsindicative of fault or operation failure situations.

The power and control system 93400 may additionally be configured toaccept various inputs from the user to dynamically control the drivemechanisms 93100 to meet a desired drug delivery rate or profile. Forexample, the power and control system 93400 may receive inputs, such asfrom partial or full activation, depression, and/or release of theactivation mechanism 9314, to set, initiate, stop, or otherwise adjustthe control of the drive mechanism 93100 via the power and controlsystem 93400 to meet the desired drug delivery rate or profile.Similarly, the power and control system 93400 may be configured toreceive such inputs to adjust the drug dose volume; to prime the drivemechanism, fluid pathway connector, and fluid conduit; and/or to start,stop, or pause operation of the drive mechanism 93100. Such inputs maybe received by the user directly acting on the drug delivery device9310, such as by use of the activation mechanism 9314 or a differentcontrol interface, or the system 93400 may be configured to receive suchinputs from a remote control device. Additionally or alternatively, suchinputs may be pre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism 9314 of the drugdelivery device 9310 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

XII.B. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9310, the fluid pathway connector 93300 isenabled to connect the sterile fluid conduit 9330 to the drug containerof the drive mechanism 93100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 93100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user.

In at least one embodiment of the present disclosure, the piercingmember of the fluid pathway connector is caused to penetrate thepierceable seal of the drug container of the drive mechanism by directaction of the user, such as by depression of the activation mechanism bythe user. For example, the activation mechanism itself may bear on thefluid pathway connector such that displacement of the activationmechanism from its original position also causes displacement of thefluid pathway connector. In one such embodiment, the fluid pathwayconnector may be substantially similar to that described inInternational Patent Application No. PCT/US2012/054861, which isincluded by reference herein in its entirety for all purposes. Accordingto such an embodiment, the connection is enabled by the user depressingthe activation mechanism and, thereby, driving the piercing memberthrough the pierceable seal, because this prevents fluid flow from thedrug container until desired by the user. In such an embodiment, acompressible sterile sleeve may be fixedly attached between the cap ofthe drug container and the connection hub of the fluid pathwayconnector. The piercing member may reside within the sterile sleeveuntil a connection between the fluid connection pathway and the drugcontainer is desired. The sterile sleeve may be sterilized to ensure thesterility of the piercing member and the fluid pathway prior toactivation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Application No.PCT/US2013/030478, for example, which is included by reference herein inits entirety for all purposes. According to such an embodiment, a drugcontainer may have a drug chamber within a barrel between a pierceableseal and a plunger seal. A drug fluid is contained in the drug chamber.Upon activation of the device by the user, a drive mechanism asserts aforce on a plunger seal contained in the drug container. As the plungerseal asserts a force on the drug fluid and any air/gas gap or bubble, acombination of pneumatic and hydraulic pressure builds by compression ofthe air/gas and drug fluid and the force is relayed to the slidingpierceable seal. The sliding pierceable seal is caused to slide towardsthe cap, causing it to be pierced by the piercing member retained withinthe integrated sterile fluid pathway connector. Accordingly, theintegrated sterile fluid pathway connector is connected (i.e., the fluidpathway is opened) by the combination pneumatic/hydraulic force of theair/gas and drug fluid within the drug chamber created by activation ofa drive mechanism. Once the integrated sterile fluid pathway connectoris connected or opened, drug fluid is permitted to flow from the drugcontainer, through the integrated sterile fluid pathway connector,sterile fluid conduit, and insertion mechanism, and into the body of theuser for drug delivery. In at least one embodiment, the fluid flowsthrough only a manifold and a cannula and/or needle of the insertionmechanism, thereby maintaining the sterility of the fluid pathway beforeand during drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 93300 and the sterile fluid conduit 9330 are providedhereinafter in later sections in reference to other embodiments.

XII.C. Insertion Mechanism

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure.

In at least one embodiment, the insertion mechanism 93200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 86B and FIG. 86C). The connection of the base to theassembly platform 9320 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9310. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9330 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9327 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane 93254 (shown in FIG. 86C).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. As shown in FIG. 86B, the lockoutpin(s) 93208 may be directly displaced by user depression of theactivation mechanism 9314. As the user disengages any safety mechanisms,such as an optional on-body sensor 9324 (shown in FIG. 86C), theactivation mechanism 9314 may be depressed to initiate the drug deliverydevice. Depression of the activation mechanism 9314 may directly causetranslation or displacement of control arm 9340 and directly orindirectly cause displacement of lockout pin(s) 93208 from their initialposition within locking windows 93202A of insertion mechanism housing93202. Displacement of the lockout pin(s) 93208 permits insertionbiasing member to decompress from its initial compressed, energizedstate. This decompression of the insertion biasing member drives theneedle and the cannula into the body of the user. At the end of theinsertion stage, the refraction biasing member is permitted to expand inthe proximal direction from its initial energized state. This axialexpansion in the proximal direction of the refraction biasing memberrefracts the needle, while maintaining the cannula in fluidcommunication with the body of the user. Accordingly, the insertionmechanism may be used to insert a needle and cannula into the user and,subsequently, retract the needle while retaining the cannula in positionfor drug delivery to the body of the user.

XII.D. Drive Mechanism

With reference to the embodiments shown in FIGS. 87 and 88, drivemechanism 93100 includes a drive housing 93130, and a drug container9350 having a cap 9352, a pierceable seal (not visible), a barrel 9358,and a plunger seal 9360. A drug chamber 9321, located within the barrel9358 between the pierceable seal and the plunger seal 9360, may containa drug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. The seals described hereinmay be comprised of a number of materials but are, in a preferredembodiment, comprised of one or more elastomers or rubbers. The drivemechanism may further include a connection mount 9354 to guide theinsertion of the piercing member of the fluid pathway connector into thebarrel 9358 of the drug container 9350. The drive mechanism 93100 mayfurther contain one or more drive biasing members, one or more releasemechanisms, and one or more guides, as are described further herein. Thecomponents of the drive mechanism function to force a fluid from thedrug container out through the pierceable seal, or preferably throughthe piercing member of the fluid pathway connector, for delivery throughthe fluid pathway connector, sterile fluid conduit, and insertionmechanism into the body of the user.

In one particular embodiment, the drive mechanism 93100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. The fluid pathway connector may beconnected through the pierceable seal prior to, concurrently with, orafter activation of the drive mechanism to permit fluid flow from thedrug container, through the fluid pathway connector, sterile fluidconduit, and insertion mechanism, and into the body of the user for drugdelivery. In at least one embodiment, the fluid flows through only amanifold and a cannula of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detailhereinafter.

Referring now to the embodiment of the drive mechanism shown in FIG. 87and FIG. 88, the drive mechanism 93100 includes a drug container 9350having a cap 9352, a pierceable seal (not visible), a barrel 9358, and aplunger seal 9360, and optionally a connection mount 9354. The drugcontainer 9350 is mounted to a distal end of a drive housing 93130.Compressed within the drive housing 93130, between the drug container9350 and the proximal end of the housing 93130, are a drive biasingmember 93122 and a piston 93110, wherein the drive biasing member 93122is configured to bear upon an interface surface 93110C of the piston93110, as described further herein. Optionally, a cover sleeve 93140 maybe utilized between the drive biasing member 93122 and the interfacesurface 93110C of the piston 93110 to, for example, promote more evendistribution of force from the drive biasing member 93122 to the piston93110, prevent buckling of the drive biasing member 93122, and/or hidebiasing member from user view. Interface surface 93110C of piston 93110is caused to rest substantially adjacent to, or in contact with, aproximal end of seal 9360.

As shown in FIG. 88, the piston 93110A, 93110B may be comprised of twocomponents and have an interface surface 93110C to contact the plungerseal. A tether, ribbon, string, or other retention strap (referred toherein as the “tether” 93512) may be connected at one end to the piston93110A, 93110B. For example, the tether 93512 may be connected to thepiston 93110A, 93110B by retention between the two components of thepiston 93110A, 93110B when assembled. The tether 93512 is connected atanother end to a winch drum 93520 of a delivery control mechanism 93500.Through the use of a motor 93530, a gear assembly, and the winch drum93520 connected to one end of the tether 93512, and the tether 93512connected at another end to the piston 93110A, 93110B, the deliverycontrol mechanism 93500 functions to control, meter, provide resistance,or otherwise prevent free axial translation of the piston 93110A, 93110Band plunger seal 9360 utilized to force a drug substance out of a drugcontainer 9350. Accordingly, the delivery control mechanism 93500 andthe drive mechanism 93100 (collectively referred to herein as the“controlled delivery drive mechanism”) together function to control therate or profile of drug delivery to the user.

Notably, the delivery control mechanisms 93500 of the present disclosuredo not drive the delivery of fluid substances from the drug chamber9321. The delivery of fluid substances from the drug chamber 9321 iscaused by the expansion of the biasing member 93122 from its initialenergized state acting upon the piston 93110A, 93110B and plunger seal9360. The delivery control mechanisms 93500 instead function to provideresistance to the free motion of the piston 93110A, 93110B and plungerseal 9360 as they are pushed by the expansion of the biasing member93122 from its initial energized state. Because the motor 93530 isutilized only to control, meter, provide resistance, or otherwiseprevent free axial translation of the plunger seal, instead of drivingthe translation of the plunger seal, a smaller and/or more energyefficient motor may be utilized by the novel embodiments of the presentdisclosure. The delivery control mechanism 93500, and specifically themotor 93530, does not drive the delivery but only controls the deliverymotion. The tether limits or otherwise restrains the motion of thepiston 93110, 93110B and plunger seal 9360, but does not apply the forcefor the delivery. According to a preferred embodiment, the controlleddelivery drive mechanisms and drug delivery devices of the presentdisclosure include a motor 93530 indirectly or directly connected to atether metering the axial translation of the piston 93110A, 93110B andplunger seal 9360, which are being driven to axially translate by thebiasing member 93122. The motor 93530 may, accordingly, be selected froma variety of electromechanical sources capable of incremental motion,such as brushed DC motors, EC motors, stepper motors, solenoids, orother technologies that can produce controlled motion. In at least oneembodiment, the motor is most preferably a stepper motor.

The components of the drive mechanism 93100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9360 of the drug container 9350. Optionally, the drive mechanism93100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9360 to, for example,ensure that substantially the entire drug dose has been delivered to theuser. For example, the plunger seal 9360, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user.

In at least one embodiment, as shown in FIG. 87 and FIG. 88, anend-of-dose status indication may be provided to the user once thestatus reader 93544 contacts or recognizes the final status trigger93512A positioned on the tether 93512 that would contact the statusreader 93544 at the end of axial travel of the piston 93110A, 93110B andplunger 9360 within the barrel 9358 of the drug container 9350. Forclarity, the tether 93512 may have one or more status triggers 93512A,such as electrical contacts, optical markings, or electromechanical pinsor recesses, which are capable of contacting or being recognized by astatus reader 93544. The status reader 93544 may be, for example, anelectrical switch reader to contact the corresponding electricalcontacts, an optical reader to recognize the corresponding opticalmarkings, or a mechanical or electromechanical reader configured tocontact corresponding pins, holes, or similar aspects on the tether. Thestatus triggers 93512A may be positioned along the tether 93512 to beread or recognized at positions which correspond with the beginning andend of drug delivery, as well as at desired increments during drugdelivery. As the drug delivery device is activated and drug delivery isbegun by release of the biasing member 93122 and the resulting forceapplied to the piston 93110A, 93110B and plunger seal 9360, the rate orprofile of drug delivery to the user is controlled by the motor 93530,gear assembly, and winch drum 93520 releasing the tether 93512 andpermitting expansion of the biasing member 93122 and axial translationof the piston 93110A, 93110B and plunger seal 9360. As this occurs, thestatus triggers 93512A of the tether 93512 are contacted or recognizedby the status reader 93544 and the status of the drive mechanism before,during, and after operation can be relayed to the power and controlsystem to provide feedback to the user. Depending on the number ofstatus triggers 93512A located on the tether 93512, the frequency of theincremental status indication may be varied as desired. As describedabove, a range of status readers 93544 may be utilized depending on thestatus triggers 93512A utilized by the system.

In a preferred embodiment, as described herein with reference to FIG.91, the status reader 93544 may apply a tensioning force to the tether93512. When the system reaches end-of-dose, the tether 93512 goes slackand the status reader 93544 is permitted to rotate about a fulcrum(shown in FIG. 91 as a cylindrical protrusion from the side of thestatus reader 93544). This rotation may operate an electrical orelectromechanical switch, for example a switch within sensor 93540,signaling slack in the tether 93512 to the power and control system93400. Additionally, the status gear 93528 may act as an encoder alongwith sensor 93540. The sensor/encoder combination is used to providefeedback of motor rotation, which in turn can be calibrated to theposition of piston 93110 when there is no slack in the tether 93512.Together, the status reader 93544 and sensor/encoder 93540 providepositional feedback, end-of-dose signal, and error indication, such asan occlusion, by observing slack in the tether 93512 prior to reachingthe expected number of motor rotations as counted by the sensor/encoder93540.

Returning now to the embodiment shown in FIG. 87 and FIG. 88, furtheraspects of the novel drive mechanism will be described with reference toFIGS. 89A-89C and 90A-90C. FIG. 89A shows an isometric view of the drivemechanism, according to at least a first embodiment, during its initiallocked stage. A fluid, such as a drug fluid, may be contained withinbarrel 9358, in a drug chamber 9321 between plunger seal 9360 andpierceable seal (not visible), for delivery to a user. The pierceableseal is adjacent or retained at least partially within cap 9352. Uponactivation by the user, a fluid pathway connector may be connected tothe drug container through the pierceable seal 9356. As described above,this fluid connection may be facilitated by a piercing member of thefluid pathway connector which pierces the pierceable seal and completesthe fluid pathway from the drug container, through the fluid pathwayconnector, the fluid conduit, the insertion mechanism, and the cannulafor delivery of the drug fluid to the body of the user. Initially, oneor more locking mechanisms (not shown) may retain the biasing member93122 in an initial energized position within piston 93110A, 93110B.Directly or indirectly upon activation of the device by the user, thelocking mechanism may be removed to permit operation of the drivemechanism. As shown in FIG. 90A, the piston 9310 and biasing member93122 are both initially in a compressed, energized state behind theplunger seal 9360. The biasing member 93122 may be maintained in thisstate until activation of the device between internal features of drivehousing 130 and interface surface 93110C of piston 93110A, 93110B. Asthe locking mechanism is removed or displaced, biasing member 93122 ispermitted to expand (i.e., decompress) axially in the distal direction(i.e., in the direction of the hatched arrow). Such expansion causes thebiasing member 93122 to act upon and distally translate interfacesurface 93110C and piston 93110, thereby distally translating plungerseal 9360 to push drug fluid out of the drug chamber 9321 of barrel9358.

As shown in FIG. 89B, such distal translation of the piston 93110A,93110B and plunger seal 9360 continues to force fluid flow out frombarrel 9358 through the pierceable seal 9356. In at least oneembodiment, an end-of-dose status indication may be provided to the useronce the status reader 93544 contacts or recognizes a status trigger93512A positioned on the tether 93512 to substantially correspond withthe end of axial travel of the piston 93110A, 93110B and plunger seal9360 within the barrel 9358 of the drug container 9350. As shown in FIG.89B, the status triggers 93512A are positioned along the tether 93512 atvarious increments, such as increments which correspond to certainvolume measurement, to provide incremental status indication to theuser. In at least one embodiment, the status reader is an optical statusreader configured to recognize the corresponding optical status triggerson the tether. As would be understood by an ordinarily skilled artisan,such optical status triggers may be markings which are recognizable bythe optical status reader. In another embodiment, the status reader is amechanical or electromechanical reader configured to physically contactcorresponding pins, holes, or similar aspects on the tether. Electricalcontacts could similarly be utilized on the tether as status indicatorswhich contact or are otherwise recognized by the correspondingelectrical status reader. The status triggers 93512A may be positionedalong the tether 93512 to be read or recognized at positions whichcorrespond with the beginning and end of drug delivery, as well as atdesired increments during drug delivery. FIG. 90B shows across-sectional view of the view shown in FIG. 89B. As shown, tether93512 passes substantially axially through the drive mechanism housing93130, the biasing member 93122, and connects to the piston 93110 A,93110B to restrict the axial translation of the piston 93110A, 93110Band the plunger seal 9360 that resides adjacent thereto.

As shown in FIG. 89C, the delivery control mechanisms 93500 of thepresent disclosure do not drive the delivery of fluid substances fromthe drug chamber 9321. The delivery of fluid substances from the drugchamber 9321 is caused by the expansion of the biasing member 93122 fromits initial energized state acting upon the piston 93110A, 93110B andplunger seal 9360. The delivery control mechanisms 93500 insteadfunction to provide resistance to the free motion of the piston 93110A,93110B and plunger seal 9360 as they are pushed by the expansion of thebiasing member 93122 from its initial energized state. As the motor93530 and the delivery control mechanisms 93500 release the tether93512, the biasing member 93122 is permitted to continue its expansionfrom its energized state and drive the piston 93110A, 93110B and plungerseal 9360 until the plunger seal 9360 has substantially contacted thepierceable seal 9356. This is visible in the cross-sectional viewprovided in FIG. 90C. At this point, substantially all of the drugsubstance has been pushed out of the drug chamber 9321 through the fluidpathway connector 93300 for drug delivery to the user. A status trigger93512A may be configured along the tether 93512 to correspond with thisposition of the piston 93110A, 93110B, such that, as the piston 93110A,93110B reaches its end of axial travel, a status trigger 93512A is reador recognized by the status reader 93544 to provide true end-of-doseindication to the user. As stated above, the status triggers 93512A maybe positioned along the tether 93512 to be read or recognized atpositions which correspond with the beginning and end of drug delivery,as well as at desired increments during drug delivery. The controlleddelivery drive mechanisms and/or drug delivery devices of the presentdisclosure may additionally enable a compliance push to ensure thatsubstantially all of the drug substance has been pushed out of the drugchamber 9321. The plunger seal 9360, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer. For example, when a pop-out plunger seal is employed, i.e., aplunger seal that is deformable from an initial state, the plunger sealmay be caused to deform or “pop-out” to provide a compliance push ofdrug fluid from the drug container, as shown in FIG. 90C. Additionallyor alternatively, an electromechanical status switch and interconnectassembly may be utilized to contact, connect, or otherwise enable atransmission to the power and control system to signal end-of-dose tothe user. For example, the status switch may be located distal to thepierceable seal 9356 and the interconnect located proximal to theplunger seal 9360 such that, upon substantially complete axialtranslation (and optional compliance push) of the plunger seal 9360within the barrel 9358, the status switch and interconnect coordinate toenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

FIG. 91 shows a perspective view of certain components of a controlleddelivery drive mechanism, according to at least one embodiment of thepresent disclosure. The controlled delivery drive mechanism incorporatesan incremental status indicator mechanism having a status reader and oneor more corresponding status triggers. In at least one embodiment, thegear assembly of the delivery control mechanism 93500 utilizes a motor93530 with pinion 93530A. The pinion 93530A contacts a first gear 93526Aof a compound gear 93526, and the second gear 93526B of the compoundgear 93526 contacts a gear aspect 93524B of a worm gear 93524. The wormaspect 93524A of the worm gear 93524 contacts a drum gear 93522 which isconnected to a winch drum 93520. The tether 93512 is at least partiallywrapped around the winch drum 93520. As the motor 93530 acts upon thegear assembly, the motion is conveyed by interfacing gear teeth of thepinion 93530A, compound gear 93526, worm gear 93524, and drum gear 93522to the winch drum 93520 to unwind the tether 93512 therefrom. Asdetailed above, unwinding the tether 93512 reduces the resistance itprovides on the piston 93110A, 93110B and permits the biasing member93122 to expand from its energized state, thereby driving the plungerseal 9360 for drug delivery. As the tether 93512 is unwound from thewinch drum 93520, a status reader 93544 may read or recognize one ormore corresponding status triggers 93512A on the tether 93512 to provideincremental status indication before, during, and after operation of thecontrolled delivery drive mechanism. As described above, a number ofstatus readers may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism shown in FIG. 91 mayutilize a mechanical status reader 93544 which is physically contactedby ridges, holes, or other aspects incrementally spaced on the tether93512 to correspond with desired status indications (e.g., volumedelivered, volume remaining, changes in delivery rates or profiles,etc.). As the status reader 93544 is contacted by the status trigger(s)93512A, the status reader 93544 causes the sensor 93540 to measure theposition of the status gear 93528 and transmit a signal to the power andcontrol system for status indication to the user. As described above,optical status readers and corresponding triggers, electromechanicalstatus readers and corresponding triggers, and/or mechanical statusreaders and corresponding triggers may all be utilized by theembodiments of the present disclosure to provide incremental statusindication to the user.

Assembly and/or manufacturing of controlled delivery drive mechanism93100, drug delivery pump 9310, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9350 may first be assembledand filled with a fluid for delivery to the user. The drug container9350 includes a cap 9352, a pierceable seal 9356, a barrel 9358, and aplunger seal 9360. The pierceable seal 9356 may be fixedly engagedbetween the cap 9352 and the barrel 9358, at a distal end of the barrel9358. The barrel 9358 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9360 from theproximal end of the barrel 9358. An optional connection mount 9354 maybe mounted to a distal end of the pierceable seal 9356. The connectionmount 9354 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9358 of the drug container 9350. Thedrug container 9350 may then be mounted to a distal end of drive housing93130.

A drive biasing member 93122 may be inserted into a distal end of thedrive housing 93130. Optionally, a cover sleeve 93140 may be insertedinto a distal end of the drive housing 130 to substantially coverbiasing member 93122. A piston may be inserted into the distal end ofthe drive housing 93130 such that it resides at least partially withinan axial pass-through of the biasing member 93122 and the biasing member93122 is permitted to contact a piston interface surface 93110C ofpiston 93110A, 93110B at the distal end of the biasing member 93122. Anoptional cover sleeve 93140 may be utilized to enclose the biasingmember 93122 and contact the piston interface surface 93110C of piston93110A, 93110B. The piston 93110A, 93110B and drive biasing member93122, and optional cover sleeve 93140, may be compressed into drivehousing 93130. Such assembly positions the drive biasing member 93122 inan initial compressed, energized state and preferably places a pistoninterface surface 93110C in contact with the proximal surface of theplunger seal 9360 within the proximal end of barrel 9358. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 93130 prior to attachment or mounting of the drug container9350. The tether 93512 is pre-connected to the proximal end of thepiston 93110A, 93110B and passed through the axial aperture of thebiasing member 93122 and drive mechanism 93130, and then wound throughthe interior of the drug delivery device with the other end of thetether 93512 wrapped around the winch drum 93520 of the delivery controlmechanism 93500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 86B.

Certain optional standard components or variations of drive mechanism93100 or drug delivery device 9310 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power themotor, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9318, as shown inFIG. 86A, to enable the user to view the operation of the drug deliverydevice 9310 or verify that drug dose has completed. Similarly, the drugdelivery device 9310 may contain an adhesive patch 9326 and a patchliner 9328 on the bottom surface of the housing 9312. The adhesive patch9326 may be utilized to adhere the drug delivery device 9310 to the bodyof the user for delivery of the drug dose. As would be readilyunderstood by one having ordinary skill in the art, the adhesive patch9326 may have an adhesive surface for adhesion of the drug deliverydevice to the body of the user. The adhesive surface of the adhesivepatch 9326 may initially be covered by a non-adhesive patch liner 9328,which is removed from the adhesive patch 9326 prior to placement of thedrug delivery device 9310 in contact with the body of the user. Removalof the patch liner 9328 may further remove the sealing membrane 93254 ofthe insertion mechanism 93200, opening the insertion mechanism to thebody of the user for drug delivery (as shown in FIG. 86C).

Similarly, one or more of the components of controlled delivery drivemechanism 93100 and drug delivery device 9310 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9310 is shown as two separate components upper housing9312A and lower housing 9312B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The novel controlleddelivery drive mechanisms of the present disclosure may be directly orindirectly activated by the user. Furthermore, the novel configurationsof the controlled delivery drive mechanism and drug delivery devices ofthe present disclosure maintain the sterility of the fluid pathwayduring storage, transportation, and through operation of the device.Because the path that the drug fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe drug container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent disclosure do not require terminal sterilization upon completionof assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connector, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a user, wherein a tetheris utilized to restrain the free axial translation of the piston. Themethod of operation of the insertion mechanism and the drug deliverydevice may be better appreciated with reference to FIGS. 89A-89C andFIGS. 90A-90C, as described above.

XIII. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 69A-73D, 80A-85C, and 86A-91 may be configured toincorporate the embodiments of the drive mechanism described below inconnection with FIGS. 92-99. The embodiments of the drive mechanismdescribed below in connection with FIGS. 92-99 may be used to replace,in its entirety or partially, the above-described drive mechanism 100,6100, 8100, 9010, 9210, or 9310, or any other drive mechanism describedherein, where appropriate.

The present disclosure provides drive mechanisms for the controlleddelivery of drug substances, drug delivery pumps with such drivemechanisms, the methods of operating such devices, and the methods ofassembling such devices. Notably, the drive mechanisms of the presentdisclosure control the rate of drug delivery by metering, providingresistance, or otherwise preventing free axial translation of theplunger seal utilized to force a drug substance out of a drug container.The novel embodiments of the present disclosure thus are capable ofdelivering drug substances at variable rates. The drive mechanisms ofthe present disclosure may be pre-configurable or dynamicallyconfigurable, such as by control by the power and control system, tomeet desired delivery rates or profiles, as explained in detail below.Additionally, the drive mechanisms of the present disclosure provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. Because the end-of-doseindication is related to the physical end of axial translation of one ormore components of the drive mechanism, the drive mechanism and drugdelivery device provide a true end-of-dose indication to the user.Through these mechanisms, confirmation of drug dose delivery canaccurately be provided to the user or administrator. Accordingly, thenovel devices of the present disclosure alleviate one or more of theproblems associated with prior art devices, such as those referred toabove.

In a first embodiment, the present disclosure provides a controlleddelivery drive mechanism which includes a drug container having a barreland a plunger seal; a drive housing within which at least initiallypartially resides a piston having an interface surface and a drive rack;and a power spring coupled, directly or indirectly, to a drive pinionwhich interfaces with drive rack of the piston to convert rotationalmovement of power spring and the drive pinion to axial translation ofthe drive rack. The piston is configured to contact and axiallytranslate the plunger seal within barrel. This configuration convertsrotational movement of the drive pinion to axial translation of thedrive rack. A regulating mechanism meters the drive pinion such that thepiston is axially translated at a controlled rate. The drug containermay contain a drug fluid within a drug chamber for drug delivery at acontrolled rate.

In another embodiment, the present disclosure provides a controlleddelivery drive mechanism having a drug container having a barrel and aplunger seal; a drive housing within which at least initially partiallyresides a linear power spring and a piston having an interface surfaceand a drive rack, wherein the linear power spring is coupled, directlyor indirectly, to the piston to convert axial force of the linear powerspring into torsional motion of a drive pinion. The piston is configuredto contact and axially translate the plunger seal within barrel. Aregulating mechanism meters the drive pinion such that the piston isaxially translated by the linear power spring at a controlled rate.

In at least one embodiment, the regulating mechanism is an escapementregulating mechanism coupled to, or acting with, the power spring. Theescapement regulating mechanism further includes a gear train having oneor more gears, a rotation shaft, and a gear transmission having one ormore gears, wherein at least one gear of the gear transmission iscapable of engaging the drive pinion such that rotation of the gearcauses rotation of the drive pinion. In a particular embodiment, theescapement regulating element further includes a lever and an escapewheel configured to engage and meter the rotational movement of the geartrain. The lever has pins and a prong, wherein the prong movably engagesa post and is configured to removably engage an impulse pin of a balancewheel, and wherein the balance wheel engages and is capable ofoscillating around a post in combination with a hair spring. The escapewheel is a compound gear having escape teeth around the circumference ofa large diameter escape gear and a small diameter gear configured toengage and meter the gear train. The metering of the drive pinion and/orthe gear train by an escapement regulating mechanism controls the rateor profile of drug delivery to a user.

In at least one embodiment, the drive mechanism utilizes a status readerconfigured to read or recognize one or more corresponding statustriggers, wherein, during operation of the drive mechanism, interactionbetween the status reader and the status triggers transmit a signal to apower and control system to provide feedback to a user. The statusreader may be an optical status reader and the corresponding statustriggers are gear teeth of a drive gear, a mechanical status reader andthe corresponding status triggers are gear teeth of the drive gear, amechanical status reader and the corresponding status triggers areexternal features of the piston and/or drive rack, or an optical statusreader and the corresponding status triggers are external features ofthe piston and/or drive rack.

In a further embodiment, the present disclosure provides a drug deliverypump having a controlled delivery drive mechanism. The drug deliverydevice includes a housing and an assembly platform, upon which anactivation mechanism, an insertion mechanism, a fluid pathway connector,a power and control system, and the controlled delivery drive mechanismmay be mounted. The drug container of the drug delivery device containsa drug fluid within a drug chamber for drug delivery at a controlledrate.

The drug delivery device may utilize the first controlled delivery drivemechanism described above in the first embodiment, which configurationutilizes a power spring and converts rotational movement of the drivepinion to axial translation of the drive rack, or the second controlleddelivery drive mechanism described above in the second embodiment, whichconfiguration utilizes a linear power spring to convert axial force intotorsional motion of a drive pinion. In either embodiment, the piston isconfigured to contact and axially translate the plunger seal withinbarrel. Each embodiment may also utilize a regulating mechanism to meterthe drive pinion such that the piston is axially translated by thelinear power spring at a controlled rate.

In at least one embodiment, the regulating mechanism is an escapementregulating mechanism coupled to, or acting with, the power spring. Theescapement regulating mechanism further includes a gear train having oneor more gears, a rotation shaft, and a gear transmission having one ormore gears, wherein at least one gear of the gear transmission iscapable of engaging the drive pinion such that rotation of the gearcauses rotation of the drive pinion. In a particular embodiment, theescapement regulating element further includes a lever and an escapewheel configured to engage and meter the rotational movement of the geartrain. The lever has pins and a prong, wherein the prong movably engagesa post and is configured to removably engage an impulse pin of a balancewheel, and wherein the balance wheel engages and is capable ofoscillating around a post in combination with a hair spring. The escapewheel is a compound gear having escape teeth around the circumference ofa large diameter escape gear and a small diameter gear configured toengage and meter the gear train. The metering of the drive pinion and/orthe gear train by an escapement regulating mechanism controls the rateor profile of drug delivery to a user.

In at least one embodiment, the drug delivery device utilizes a statusreader configured to read or recognize one or more corresponding statustriggers, wherein, during operation of the drive mechanism, interactionbetween the status reader and the status triggers transmit a signal to apower and control system to provide feedback to a user. The statusreader may be an optical status reader and the corresponding statustriggers are gear teeth of a drive gear, a mechanical status reader andthe corresponding status triggers are gear teeth of the drive gear, amechanical status reader and the corresponding status triggers areexternal features of the piston and/or drive rack, or an optical statusreader and the corresponding status triggers are external features ofthe piston and/or drive rack.

The present disclosure provides drive mechanisms for the controlleddelivery of drug substances and drug delivery pumps which incorporatesuch drive mechanisms. The drive mechanisms of the present disclosurecontrol the rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container and, thus, are capableof delivering drug substances at variable rates and/or deliveryprofiles. Additionally, the drive mechanisms of the present disclosureprovide integrated status indication features which provide feedback tothe user before, during, and after drug delivery. For example, the usermay be provided an initial feedback to identify that the system isoperational and ready for drug delivery. Upon activation, the system maythen provide one or more drug delivery status indications to the user.At completion of drug delivery, the variable rate drive mechanism anddrug delivery device may provide an end-of-dose indication.

The novel devices of the present disclosure provide variable ratecontrolled delivery drive mechanisms with integrated status indicationand drug delivery pumps which incorporate such drive mechanisms. Suchdevices are safe and easy to use, and are aesthetically andergonomically appealing for self-administering patients. The devicesdescribed herein incorporate features which make activation, operation,and lock-out of the device simple for even untrained users. The noveldevices of the present disclosure provide these desirable featureswithout any of the problems associated with known prior art devices.Certain non-limiting embodiments of the novel drug delivery pumps, drivemechanisms, and their respective components are described further hereinwith reference to the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.92A-92C show an exemplary drug delivery device or drug delivery deviceaccording to at least one embodiment of the present disclosure. The drugdelivery device may be utilized to administer delivery of a drugtreatment into a body of a user. As shown in FIGS. 92A-92C, the drugdelivery device 9410 includes a pump housing 9412. Pump housing 9412 mayinclude one or more housing subcomponents which are fixedly engageableto facilitate easier manufacturing, assembly, and operation of the drugdelivery device. For example, drug delivery device 9410 includes a pumphousing 9412 which includes an upper housing 9412A and a lower housing9412B. The drug delivery device may further include an activationmechanism 9414, a status indicator 9416, and a window 9418. Window 9418may be any translucent or transmissive surface through which theoperation of the drug delivery device may be viewed. As shown in FIG.92B, drug delivery device further includes assembly platform 9420,sterile fluid conduit 9430, drive mechanism 94100 having drug container9450, insertion mechanism 94200, fluid pathway connector 94300, andpower and control system 94400. One or more of the components of suchdrug delivery devices may be modular in that they may be, for example,pre-assembled as separate components and configured into position ontothe assembly platform 9420 of the drug delivery device 9410 duringmanufacturing.

The pump housing 9412 contains all of the device components and providesa means of removably attaching the device 9410 to the skin of the user.The pump housing 9412 also provides protection to the interiorcomponents of the device 9410 against environmental influences. The pumphousing 9412 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9412 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9412 may include certaincomponents, such as status indicator 9416 and window 9418, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9410 provides anactivation mechanism 9414 that is displaced by the user to trigger thestart command to the power and control system 94400. In a preferredembodiment, the activation mechanism is a start button 9414 that islocated through the pump housing 9412, such as through an aperturebetween upper housing 9412A and lower housing 9412B, and which contactsa control arm 9440 of the power and control system 94400. In at leastone embodiment, the start button 9414 may be a push button, and in otherembodiments, may be an on/off switch, a toggle, or any similaractivation feature known in the art. The pump housing 9412 also providesa status indicator 9416 and a window 9418. In other embodiments, one ormore of the activation mechanism 9414, the status indicator 9416, thewindow 9418, and combinations thereof may be provided on the upperhousing 9412A or the lower housing 9412B such as, for example, on a sidevisible to the user when the drug delivery device 9410 is placed on thebody of the user. Housing 9412 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device is configured such that, upon activation by a userby depression of the activation mechanism, the drug delivery device isinitiated to: insert a fluid pathway into the user; enable, connect, oropen necessary connections between a drug container, a fluid pathway,and a sterile fluid conduit; and force drug fluid stored in the drugcontainer through the fluid pathway and fluid conduit for delivery intoa user. One or more optional safety mechanisms may be utilized, forexample, to prevent premature activation of the drug delivery device.For example, an optional on-body sensor 9424 (shown in FIG. 92C) may beprovided in one embodiment as a safety feature to ensure that the powerand control system 94400, or the activation mechanism, cannot be engagedunless the drug delivery device 9410 is in contact with the body of theuser. In one such embodiment, the on-body sensor 9424 is located on thebottom of lower housing 9412B where it may come in contact with theuser's body. Upon displacement of the on-body sensor 9424, depression ofthe activation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor 9424 is a mechanical safety mechanism,such as for example a mechanical lock out, that prevents triggering ofthe drug delivery device 9410 by the activation mechanism 9414. Inanother embodiment, the on-body sensor may be an electro-mechanicalsensor such as a mechanical lock out that sends a signal to the powerand control system 94400 to permit activation. In still otherembodiments, the on-body sensor can be electrically based such as, forexample, a capacitive- or impedance-based sensor which must detecttissue before permitting activation of the power and control system94400. These concepts are not mutually exclusive and one or morecombinations may be utilized within the breadth of the presentdisclosure to prevent, for example, premature activation of the drugdelivery device. In a preferred embodiment, the drug delivery device9410 utilizes one or more mechanical on-body sensors. Additionalintegrated safety mechanisms are described herein with reference toother components of the novel drug delivery devices.

XIII.A. Power and Control System

The power and control system 94400 includes a power source, whichprovides the energy for various electrical components within the drugdelivery device, one or more feedback mechanisms, a microcontroller, acircuit board, one or more conductive pads, and one or moreinterconnects. Other components commonly used in such electrical systemsmay also be included, as would be appreciated by one having ordinaryskill in the art. The one or more feedback mechanisms may include, forexample, audible alarms such as piezo alarms and/or light indicatorssuch as light emitting diodes (LEDs). The microcontroller may be, forexample, a microprocessor. The power and control system 94400 controlsseveral device interactions with the user and interfaces with the drivemechanism 94100. In one embodiment, the power and control system 94400interfaces with the control arm 9440 to identify when the on-body sensor9424 and/or the activation mechanism 9414 have been activated. The powerand control system 94400 may also interface with the status indicator9416 of the pump housing 9412, which may be a transmissive ortranslucent material which permits light transfer, to provide visualfeedback to the user. The power and control system 94400 interfaces withthe drive mechanism 94100 through one or more interconnects to relaystatus indication, such as activation, drug delivery, and end-of-dose,to the user. Such status indication may be presented to the user viaauditory tones, such as through the audible alarms, and/or via visualindicators, such as through the LEDs. In a preferred embodiment, thecontrol interfaces between the power and control system and the othercomponents of the drug delivery device are not engaged or connecteduntil activation by the user. This is a desirable safety feature thatprevents accidental operation of the drug delivery device and mayadditionally maintain the energy contained in the power source duringstorage, transportation, and the like.

The power and control system 94400 may be configured to provide a numberof different status indicators to the user. For example, the power andcontrol system 94400 may be configured such that after the on-bodysensor and/or trigger mechanism have been pressed, the power and controlsystem 94400 provides a ready-to-start status signal via the statusindicator 9416 if device start-up checks provide no errors. Afterproviding the ready-to-start status signal and, in an embodiment withthe optional on-body sensor, if the on-body sensor remains in contactwith the body of the user, the power and control system 94400 will powerthe drive mechanism 94100 to begin delivery of the drug treatmentthrough the fluid pathway connector 94300 and sterile fluid conduit9430. In a preferred embodiment of the present disclosure, the insertionmechanism 94200 and the fluid pathway connector 94300 may be caused toactivate directly by user operation of the activation mechanism 9414.During the drug delivery process, the power and control system 94400 isconfigured to provide a dispensing status signal via the statusindicator 9416. After the drug has been administered into the body ofthe user and after the end of any additional dwell time, to ensure thatsubstantially the entire dose has been delivered to the user, the powerand control system 94400 may provide an okay-to-remove status signal viathe status indicator 9416. This may be independently verified by theuser by viewing the drive mechanism and drug dose delivery through thewindow 9418 of the pump housing 9412. Additionally, the power andcontrol system 94400 may be configured to provide one or more alertsignals via the status indicator 9416, such as for example alertsindicative of fault or operation failure situations.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism 9414 of the drugdelivery device 9410 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

XIII.B. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9410, the fluid pathway connector 94300 isenabled to connect the sterile fluid conduit 9430 to the drug containerof the drive mechanism 94100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 94100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user.

In at least one embodiment of the present disclosure, the piercingmember of the fluid pathway connector is caused to penetrate thepierceable seal of the drug container of the drive mechanism by directaction of the user, such as by depression of the activation mechanism bythe user. For example, the activation mechanism itself may bear on thefluid pathway connector such that displacement of the activationmechanism from its original position also causes displacement of thefluid pathway connector. In one such embodiment, the fluid pathwayconnector may be substantially similar to that described inInternational Patent Application No. PCT/US2012/054861, which isincluded by reference herein in its entirety for all purposes. Accordingto such an embodiment, the connection is enabled by the user depressingthe activation mechanism and, thereby, driving the piercing memberthrough the pierceable seal, because this prevents fluid flow from thedrug container until desired by the user. In such an embodiment, acompressible sterile sleeve may be fixedly attached between the cap ofthe drug container and the connection hub of the fluid pathwayconnector. The piercing member may reside within the sterile sleeveuntil a connection between the fluid connection pathway and the drugcontainer is desired. The sterile sleeve may be sterilized to ensure thesterility of the piercing member and the fluid pathway prior toactivation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Application No.PCT/US2013/030478, for example, which is included by reference herein inits entirety for all purposes. According to such an embodiment, a drugcontainer may have a drug chamber within a barrel between a pierceableseal and a plunger seal. A drug fluid is contained in the drug chamber.Upon activation of the device by the user, a drive mechanism asserts aforce on a plunger seal contained in the drug container. As the plungerseal asserts a force on the drug fluid and any air/gas gap or bubble, acombination of pneumatic and hydraulic pressure builds by compression ofthe air/gas and drug fluid and the force is relayed to the slidingpierceable seal. The sliding pierceable seal is caused to slide towardsthe cap, causing it to be pierced by the piercing member retained withinthe integrated sterile fluid pathway connector. Accordingly, theintegrated sterile fluid pathway connector is connected (i.e., the fluidpathway is opened) by the combination pneumatic/hydraulic force of theair/gas and drug fluid within the drug chamber created by activation ofa drive mechanism. Once the integrated sterile fluid pathway connectoris connected or opened, drug fluid is permitted to flow from the drugcontainer, through the integrated sterile fluid pathway connector,sterile fluid conduit, and insertion mechanism, and into the body of theuser for drug delivery. In at least one embodiment, the fluid flowsthrough only a manifold and a cannula and/or needle of the insertionmechanism, thereby maintaining the sterility of the fluid pathway beforeand during drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 94300 and the sterile fluid conduit 9430 are providedhereinafter in later sections in reference to other embodiments.

XIII.C. Insertion Mechanism:

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure.

In at least one embodiment, the insertion mechanism 94200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 92B and FIG. 92C). The connection of the base to theassembly platform 9420 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9410. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9430 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9427 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane 94254 (shown in FIG. 92C).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. As shown in FIG. 92B, the lockoutpin(s) 94208 may be directly displaced by user depression of theactivation mechanism 9414. As the user disengages any safety mechanisms,such as an optional on-body sensor 9424 (shown in FIG. 92C), theactivation mechanism 9414 may be depressed to initiate the drug deliverydevice. Depression of the activation mechanism 9414 may directly causetranslation or displacement of control arm 9440 and directly orindirectly cause displacement of lockout pin(s) 94208 from their initialposition within locking windows 94202A of insertion mechanism housing94202. Displacement of the lockout pin(s) 94208 permits insertionbiasing member to decompress from its initial compressed, energizedstate. This decompression of the insertion biasing member drives theneedle and the cannula into the body of the user. At the end of theinsertion stage, the refraction biasing member is permitted to expand inthe proximal direction from its initial energized state. This axialexpansion in the proximal direction of the refraction biasing memberrefracts the needle, while maintaining the cannula in fluidcommunication with the body of the user. Accordingly, the insertionmechanism may be used to insert a needle and cannula into the user and,subsequently, retract the needle while retaining the cannula in positionfor drug delivery to the body of the user.

XIII.D. Drive Mechanism:

With reference to the embodiments shown in FIGS. 93 and 94, drivemechanism 94100 includes a drive housing 94130, and a drug container9450 having a cap 9452, a pierceable seal 9456, a barrel 9458, and aplunger seal 9460. A drug chamber 9421, located within the barrel 9458between the pierceable seal and the plunger seal 9460, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. The seals described hereinmay be comprised of a number of materials but are, in a preferredembodiment, comprised of one or more elastomers or rubbers. The drivemechanism may further include a connection mount 9454 to guide theinsertion of the piercing member of the fluid pathway connector into thebarrel 9458 of the drug container 9450. The drive mechanism 94100 mayfurther contain one or more drive biasing members, one or more releasemechanisms, and one or more guides, as are described further herein. Thecomponents of the drive mechanism function to force a fluid from thedrug container out through the pierceable seal, or preferably throughthe piercing member of the fluid pathway connector, for delivery throughthe fluid pathway connector, sterile fluid conduit, and insertionmechanism into the body of the user.

In one particular embodiment, the drive mechanism 94100 employs one ormore springs as the drive biasing member(s). Upon activation of the drugdelivery device by the user, the power and control system may beactuated to directly or indirectly release the spring(s) from anenergized state. Upon release, the spring(s) may be utilized, directlyor indirectly, to drive the plunger seal and force the fluid drug out ofthe drug container. More specifically, the spring may be utilized,directly or indirectly, to drive a piston which, in turn, acts upon theplunger seal to force the fluid drug out of the drug container. Thefluid pathway connector may be connected through the pierceable sealprior to, concurrently with, or after activation of the drive mechanismto permit fluid flow from the drug container, through the fluid pathwayconnector, sterile fluid conduit, and insertion mechanism, and into thebody of the user for drug delivery. In at least one embodiment, thefluid flows through only a manifold and a cannula of the insertionmechanism, thereby maintaining the sterility of the fluid pathway beforeand during drug delivery. Such components and their functions aredescribed in further detail hereinafter.

Referring now to the embodiment of the drive mechanism shown in FIG. 93and FIG. 9494, the drive mechanism 94100 includes a drug container 9450having a cap 9452, a pierceable seal 9456, a barrel 9458, and a plungerseal 9460, and optionally a connection mount 9454. The drug container9450 is mounted to a distal end of a drive housing 94130. A piston 94110having an interface surface 94110C and a drive rack 94110A is retainedat least partially within the drive housing 94130, between the drugcontainer 9450 and the proximal end of the housing 94130. Optionally, acover sleeve may be utilized to engage the piston 94110 and cover thedrive rack 94110A to hide such components from user view upon expansionfrom its initial position. The cover sleeve may be configured to engageand slide upon the piston 94110, between the piston 94110 and the distalend of the drive mechanism housing 94130 to hide the drive rack 94110Afrom user view upon expansion from its initial energized state.

As shown in FIGS. 94A and 94B, the controlled delivery drive mechanism94100 of the present disclosure may utilize a power spring 94122coupled, directly or indirectly to the drive pinion 94120 whichinterfaces with drive rack 94110A of the piston 94110 to convertrotational movement of the drive pinion 94120 to axial translation ofthe drive rack 94110A, thereby pushing plunger seal 9460 within barrel9458 to force a fluid from drug chamber 9421. Notably, the power spring94122 imparts torque to a gear assembly, such as the drive pinion 94120,which pushes a plunger seal 9460 within barrel 9458 which contains thedrug substance. Alternatively a linear power spring 941122 can becoupled directly or indirectly to the piston 94110 with drive rack94110A to convert axial force into torsional motion which is coupled todrive pinion 94120 and into the regulating mechanism 94500, as shown inFIG. 99. In both configurations, the plunger seal 9460 advances into thedrug container 9450, the drug substance is dispensed through the sterilepathway connection 94300, conduit 9430, insertion mechanism 94200, andinto the body of the user for drug delivery. Certain reaction forces onthe plunger seal, such as hydraulic resistance from the flow of the drugsubstance and friction of the plunger seal against the barrel, can varysignificantly. As such, it is desirable to have a regulating mechanism94500 in the drive mechanism 94100 which keeps a constant rate ofdelivery as these forces vary. In the embodiments of the presentdisclosure, the regulating mechanism 94500 is an escapement regulatingmechanism. The escapement regulating mechanism retards or restrains thegear assembly, only allowing it to advance at a regulated or desirablerate. In such a configuration, the power spring 94122 is designed tosupply sufficient torque to overcome worst case variations in thehydraulic and frictional forces. In theory, any excess force whichoccurs under more nominal reaction force conditions is absorbed by theescapement regulating mechanism and the delivery rate remains constant.

In at least one embodiment of the present disclosure, the drivemechanism 94100 utilizes an escapement regulating element 94500 and apower spring 94122. The power spring 94122 is configured to providerotational movement, around an axis “B”, to one or more gears 94512,94514, 94516 of a gear train 94510 (and/or to gear 94522 of geartransmission 94550). Each of the gears 94512, 94514, 94516 may be, forexample, compound gears having a small diameter gear attached at ashared center point to a large diameter gear. For example first compoundgear 94512 has small diameter gear 94512B (not visible) attached tolarge diameter gear 94512A. The small diameter gear of each compoundgear engages the large diameter gear, for example, of the next compoundgear in the gear train 94510 such that rotational movement of the firstcompound gear 94512 is conveyed by engagement of the gears (such as byengagement of corresponding gear teeth) to the second compound gear94514, and so on through the gear train 94510. Such rotational movementof the gear train 94510 may be conveyed by a rotation shaft 94518 to agear transmission 94550 having one or more gears, including drive gear94520. For example, the gear transmission 94550 may include gear 94522and gear 94524 in addition to drive gear 94520. The drive gear 94520 isconnected to drive pinion 94120 (such as by connection protrusion94120A) such that rotation of the drive gear 94520 causes rotation ofthe drive pinion 94120. The drive pinion 94120 is configured to engagethe drive rack 94110A of the piston 94110 to convert rotational movementof the drive pinion 94120 to axial translation of the drive rack 94110A,thereby pushing plunger seal 9460 within barrel 9458 to force a fluidfrom drug chamber 9421. The rotational movement of the drive gear 94520,and thus the axial translation of the drive rack 94110A and plunger seal9460, are metered, restrained, or otherwise prevented from free axialtranslation by other components of the escapement regulating element94500, as described herein.

In at least one embodiment of the present disclosure, the rotation shaft94518 is keyed to both the first compound gear 94512 and the first gear94522 of the gear transmission 94550. This configuration permitsrotational movement of the first compound gear 94512, which is in directrotational alignment and/or relationship with the power spring 94122, tobe keyed and cause power transfer and rotation of the gear transmission94550 (such as at gear 94522). In this configuration, at least some ofpower from the power spring 94122 is directed for use in axiallytranslating the drive rack 94110A of the piston 94110 and the plungerseal 9460; while at least a portion of the power from the power spring94122 is directed for use by the escape wheel 94562, balance wheel94566, hair spring 94568, and lever 94564 components of the escapementregulating element 500. Accordingly, while the power spring providesforce used for axial translation of the plunger seal 9460, it alsopowers the escapement regulating element 94500 which functions to meteror restrain the force provided for such axial translation. The compoundgear structure of the gear train 94510 permits the splitting of theforce provided by the power spring 94122. Some of the power from thepower spring 94122 is transferred directly to gear 94522, rotation shaft94518, and first gear 94522 of the gear transmission 94550; while someof the power is transferred to gear 94514, gear 94516, lever 94564, andescape wheel 94562, for regulation or metering by interaction with thebalance wheel 94566 and hair spring 94568, to permit a small diametergear 94562B of the escape wheel 94562 to regulate or meter the geartrain 94510.

The escapement regulating element 94500 further includes an escape wheel94562 and a lever 94564. The escape wheel 94562 is a compound gearhaving escape teeth around the circumference of a large diameter escapegear 94562A and a small diameter gear 94562B (not visible) configured toengage the gear train 94510 and meter, restrain, or otherwise preventfree rotational movement thereof. The lever 94564 has pins 94564A,B andprong 94564C. Prong 94564C movably engages a post 94566A and isconfigured to removably engage an impulse pin 94566B of a balance wheel94566. The balance wheel 94566 engages and functions as an oscillatoraround a pivot point 94564D in combination with a hair spring 94568. Thepower spring 94122 may be retained or braced within a winder 94502 in amanner that permits the power spring 94122 to rotationally move freelywithin the winder 94502. The gear train 94510, escape wheel 94562,balance wheel 94566, hair spring 94568, and lever 94564 may be mountedon and able to freely rotate or move on a plate 94504. Similarly, geartransmission 94550 may be mounted on and able to freely rotate on aplatform 94506. The winder 94502, plate 94504, and platform 94506 mayutilize one or more spacer columns to maintain the desired spacingbetween components and one or more pivot pins upon which the componentsmay be mounted and freely rotated.

The function of the escape wheel 94562, balance wheel 94566, hair spring94568, and lever 94564 components of the escapement regulating element94500 are explained with reference to FIG. 94B and FIGS. 95A-95H. Theescape wheel 94562 is a compound gear having escape teeth around thecircumference of a large diameter escape gear 94562A and a smalldiameter gear 94562B (not visible) configured to engage the gear train94510 and meter, restrain, or otherwise prevent free rotational movementthereof. The lever 94564 has pins 94564A,B and prong 94564C. Prong94564C movably engages a post 94566A and is configured to removablyengage an impulse pin 94566B of a balance wheel 94566. The balance wheel94566 engages and functions as an oscillator around a pivot point 94564Din combination with a hair spring 94568. The escape wheel 94562 andlever 94564 may initially be in an activation position, as shown in FIG.95A. The escape wheel 94562 and lever 94564 generally function toperform two steps, termed the locking action and the impulse action.These two actions are illustrated in FIG. 95B and FIG. 95C,respectively, and in which the gear train 94510 is applying a clockwisetorque on the escape wheel 94562. In the locking action, one of twolever pins 94564A,B blocks escape wheel 94562 rotation on the radialface of a tooth on the escape gear 94562A. This locks the gear train94510 between impulse actions. In the impulse action, a lever pin94564A,B slides up to this tooth face due to action of the balance wheel94566 on the lever 94564. The escape wheel becomes unlocked and doesmechanical work on the lever pin 94564A, B via a sliding action, whichin turn imparts kinetic energy to the balance wheel 94566. The lever94564 pivots upon a pivot point 94564D until the opposite pin 94564A,Bengages with an escape wheel tooth on the escape gear 94562A, and thelocked state is re-entered after a half tooth advance of the escapewheel 94562. The transition from locking action to impulse action istriggered by the balance wheel 94566, which functions as an oscillatorin combination with the hair spring 94568. It cycles at a naturalfrequency that serves as the rate control. The balance wheel 94566contains an impulse pin 94566B which interacts with the lever 94564 atprong 94564C. For the impulse phase depicted in FIG. 95C, a clockwisemoment on the lever 94564 exerts a counterclockwise moment on thebalance wheel 94566, adding to its kinetic energy. The balance wheel94566 rotates until its kinetic energy is absorbed by the hair spring94568. It stops, reverses, and reengages the impulse pin 94566B with thelever 94564. A complete cycle is shown in the transition between FIGS.95D-95H.

To unlock the escapement regulating mechanism 94500, the balance wheel94566 must have enough kinetic energy to drag the lever pin 94564A,B upthe face of the tooth of the escape gear 94562A of the escape wheel94562. If the impulse action adds less energy than is lost to friction,the balance wheel 94566 will rotate less and less and finally stall,locking the escapement regulating mechanism 94500. If the escapementstops in this way under load, it will not restart easily. To beself-starting, the hair spring 94568 must align the lever 94564 alongthe axis connecting the pivot of the escape wheel 94562 and the pivot ofthe balance wheel 94566, as shown in FIG. 95A. The lever pins 94564A,Bwill be positioned so that a bevel tooth face can immediately start animpulse action upon application of a drive torque. This alignment canoccur only with the escapement regulating mechanism 94500 in an unloadedstate. The power spring 94122 torque must be isolated from theescapement regulating mechanism 94500 until the start of delivery. Thisaction may be initiated by a user imparting a force on an activationmechanism and, directly or indirectly through a power and control system94400, applying a drive torque to start the initial impulse action. Oncethe escapement regulating mechanism 94500 is initiated, it can beeffectively utilized to meter, restrain, or otherwise prevent freerotational movement of the gear train 94510, gear transmission 94550,drive gear 94520 and drive pinion 94120, and, thus, axial translation ofthe drive rack 94110A and plunger seal 9460. In a particular embodiment,the escape wheel 94562 is a compound gear having escape teeth around thecircumference of a large diameter escape gear 94562A and a smalldiameter gear 94562B (not visible). The small diameter gear 94562B ofthe escape wheel 94562 engages the drive train 94510, which engages withgear transmission 94550 through rotation shaft 94518. This novelconfiguration directly permits the escape wheel 94562 to regulate therotation of the drive train 94510 imparted by the power spring 94122,which then efficiently regulates the drive transmission 94550, drivegear 94520, drive pinion 94120, and drive rack 94110A of the piston94110.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement and,thus, axial translation of the components of the controlled deliverydrive mechanism 94100. Accordingly, the escapement regulating mechanism94500 only controls the motion of the drive mechanism, but does notapply the force for the drug delivery. One or more additional biasingmembers, such as compression springs, may be utilized to drive or assistthe driving of the piston 94110 (as shown in FIG. 99). For example, acompression spring may be utilize within the drive housing 94130 forthis purpose, with the power spring 94122 partly driving the piston 110and plunger seal 9460 and partly driving the escapement regulatingelement 94500 to perform the metering as described above. Accordingly,the means to control flow is separate from the load on the piston 94110and the plunger seal 9460. While the power spring 94122 applies theforce that is utilized to drive the piston 94110 and plunger seal 9460for drug delivery, the escapement regulating mechanism 94500 onlycontrols, meters, or regulates such action. A mechanical timing system,such as the escapement regulating mechanism described herein, may beutilized to allow the piston 94110 and plunger seal 9460 to translateaxially a controlled distance, or a controlled volume, and may beutilized to meet a desired delivery rate or profile. The timing systemcan be controlled by quartz timing instead of mechanical timing, aswould be appreciated by one having ordinary skill in the art. For quartztiming, a battery provides power to a microchip and circuit. The quartzcrystal oscillates at a precise frequency. Alternate electrical timingmechanisms such as, for example, RC timing mechanisms, may also be used,including clock functions commonly found in microprocessors. Dependingon the period that the delivery is planned to occur over, the microchipdrives a motor based on a number of quartz crystal oscillations or othertiming signals. The motor releases motion of a drive train, drivetransmission, and/or drive rack, to control the axial translation of aplunger in a similar manner as described herein for the mechanicaltiming system.

The drive mechanism 94100 having an escapement regulating mechanism94500 functions to control the rate of drug delivery forced by the axialtranslation of a piston 94110 and a plunger seal 9460 within a barrel9458 of a drug container 9450. This is shown in the transition fromFIGS. 96A-96C and FIGS. 97A-97C. As described above, the power spring94122 imparts a force to the drive mechanism which is regulated,metered, or otherwise controlled by the escapement regulating mechanism94500 to control the rate of axial translation of the piston 94110 andplunger seal 9460 for drug delivery. Upon initiation by the user, thepower spring 94122 is permitted to apply a force or torque to the systemwhich is regulated by the escapement regulating mechanism 94500. Thiscauses the drive mechanism shown in FIG. 96A and FIG. 97A to activateand permit metered axial translation of the piston 94110 and plungerseal 9460 in the distal direction within a barrel 9458 (i.e., in thedirection of the hatched arrow). This metered activity continues throughdrug delivery at a controlled rate or drug delivery profile, as shown inFIG. 96B and FIG. 97B, until substantially all of the drug fluid hasbeen dispensed from drug chamber 9421 through the sterile pathwayconnection 94300, as shown in FIG. 96C and FIG. 97C.

The components of the drive mechanism 94100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9460 of the drug container 9450. Optionally, the drive mechanism94100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9460 to, for example,ensure that substantially the entire drug dose has been delivered to theuser. For example, the plunger seal 9460, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer. The plunger seal 9460, itself, may have some compressibilitypermitting a compliance push of drug fluid from the drug container. Forexample, when a pop-out plunger seal is employed, i.e., a plunger sealthat is deformable from an initial state, the plunger seal may be causedto deform or “pop-out” to provide a compliance push of drug fluid fromthe drug container. Similarly, an optional cover sleeve may be utilizedto hide the visibility of the drive rack 94110A and other internalcomponents from the user as the piston 94110 is axially translatedwithin the barrel 58.

The novel variable rate drive mechanisms of the present disclosure mayoptionally integrate status indication into the drug dose delivery. Byuse of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user. Additionally oralternatively, an electromechanical status switch and interconnectassembly may be utilized to contact, connect, or otherwise enable atransmission to the power and control system to signal end-of-dose tothe user. For example, the status switch may be located distal to thepierceable seal 9456 and the interconnect located proximal to theplunger seal 9460 such that, upon substantially complete axialtranslation (and the optional compliance push) of the plunger seal 9460within the barrel 9458, the status switch and interconnect coordinate toenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

In at least one embodiment, as shown in FIG. 98, incremental statusindication may be provide to the user by reading or recognizing therotational movement of drive gear 94520. As the drive gear 94520rotates, a status reader 94600 may read or recognize one or morecorresponding status triggers on the drive gear 94520 to provideincremental status indication before, during, and after operation of thevariable rate controlled delivery drive mechanism. A number of statusreaders may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism shown in FIG. 98 mayutilize a mechanical status reader 94600 which is physically contactedby gear teeth of the drive gear 9420. As the status reader 94600 iscontacted by the status trigger(s), which in this exemplary embodimentmay be the gear teeth of the drive gear 94520 (or holes, pins, ridges,markings, electrical contacts, or the like, upon the drive gear 94520),the status reader 94600 measures the rotational position of the drivegear 94520 and transmits a signal to the power and control system forstatus indication to the user. Additionally or alternatively, the drivemechanism shown in FIG. 98 may utilize an optical status reader 94600.The optical status reader 94600 may be, for example, a light beam thatis capable of recognizing a motion and transmitting a signal to thepower and control system. For example, the drive mechanism may utilizean optical status reader 94600 that is configured to recognize motion ofthe gear teeth of the drive gear 94520 (or holes, pins, ridges,markings, electrical contacts, or the like, upon the drive gear 94520).Similarly, the status reader 94600 may be an electrical switchconfigured to recognize electrical contacts on drive gear 94520. In anyof these embodiments, sensor 94602 may be utilized to then relay asignal to the power and control system 94400 to provide feedback to theuser.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to the user.While the drive mechanisms of the present disclosure are described withreference to the gear transmission, gear train, and escapementregulating mechanism shown in FIG. 98, a range of configurations may beutilized for these components with the appropriate gear reduction basedon the load and power spring chosen would be acceptable and capable ofbeing employed within the embodiments of the present disclosure, aswould readily be appreciated by an ordinarily skilled artisan.Accordingly, the embodiments of the present disclosure are not limitedto the specific gear transmission, gear train, and escapement regulatingmechanism described herein, which is provided as an exemplary embodimentof such mechanisms for employment within the controlled delivery drivemechanisms and drug delivery pumps.

Returning now to the embodiments shown in FIGS. 96A-96C and FIGS.97A-97C, a fluid, such as a drug fluid, may be contained within barrel9458, in a drug chamber 9421, between plunger seal 9460 and pierceableseal 9456, for delivery to a user. The pierceable seal is adjacent orretained at least partially within cap 9452. Upon activation by theuser, a fluid pathway connector may be connected to the drug containerthrough the pierceable seal. As described above, this fluid connectionmay be facilitated by a piercing member of the fluid pathway connectorwhich pierces the pierceable seal and completes the fluid pathway fromthe drug container, through the fluid pathway connector, the fluidconduit, the insertion mechanism, and the cannula for delivery of thedrug fluid to the body of the user. Distal translation of the piston94110 and plunger seal 9460, but the drive mechanisms and regulatingmechanisms described herein, continues to force fluid flow out frombarrel 9458 through pierceable seal 9456. In at least one embodiment, anend-of-dose status indication may be provided to the user once thestatus reader recognizes a status trigger positioned on the drive gearto substantially correspond with the end of axial travel of the piston94110 and plunger seal 9460. The novel escapement regulating mechanism94500 and drive mechanisms 94100 of the present disclosure thus permit,meter, or otherwise restrain the free axial expansion of the biasingmember 94122 to control the rate or profile of drug delivery. The novelembodiments of the present disclosure also thus provide incrementalstatus indication to the user.

Assembly and/or manufacturing of variable rate controlled delivery drivemechanism 94100, drug delivery pump 9410, or any of the individualcomponents may utilize a number of known materials and methodologies inthe art. For example, a number of known cleaning fluids such asisopropyl alcohol and hexane may be used to clean the components and/orthe devices. A number of known adhesives or glues may similarly beemployed in the manufacturing process. Additionally, knownsiliconization and/or lubrication fluids and processes may be employedduring the manufacture of the novel components and devices. Furthermore,known sterilization processes may be employed at one or more of themanufacturing or assembly stages to ensure the sterility of the finalproduct.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9450 may first be assembledand filled with a fluid for delivery to the user. The drug container9450 includes a cap 9452, a pierceable seal 9456, a barrel 9458, and aplunger seal 9460. The pierceable seal 9456 may be fixedly engagedbetween the cap 9452 and the barrel 9458, at a distal end of the barrel9458. The barrel 9458 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9460 from theproximal end of the barrel 9458. An optional connection mount 9454 maybe mounted to a distal end of the pierceable seal 9456. The connectionmount 9454 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9458 of the drug container 9450. Thedrug container 9450 may then be mounted to a distal end of drive housing94130. The piston 94110 having a drive rack 94110A may be mounted intothe drive mechanism housing 94130 and connected to drive pinion 94120and gear drive gear 94520. The drive pinion 94120 is placed in positionadjacent the drive mechanism housing 94130 such that it extends at leastpartly into the drive housing 94130 to engage the drive rack 94110A foroperation.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 92B.

Certain optional standard components or variations of drive mechanism94100, or drug delivery device 9410, are contemplated while remainingwithin the breadth and scope of the present disclosure. For example,upper or lower housings may optionally contain one or more transparentor translucent windows 9418, as shown in FIG. 92A, to enable the user toview the operation of the drug delivery device 9410 or verify that drugdose has completed. Similarly, the drug delivery device 9410 may containan adhesive patch 9426 and a patch liner 9428 on the bottom surface ofthe housing 9412. The adhesive patch 9426 may be utilized to adhere thedrug delivery device 9410 to the body of the user for delivery of thedrug dose. As would be readily understood by one having ordinary skillin the art, the adhesive patch 9426 may have an adhesive surface foradhesion of the drug delivery device to the body of the user. Theadhesive surface of the adhesive patch 9426 may initially be covered bya non-adhesive patch liner 9428, which is removed from the adhesivepatch 9426 prior to placement of the drug delivery device 10 in contactwith the body of the user. Removal of the patch liner 9428 may furtherremove the sealing membrane 94254 of the insertion mechanism 94200,opening the insertion mechanism to the body of the user for drugdelivery (as shown in FIG. 92C).

Similarly, one or more of the components of controlled delivery drivemechanism 94100 and drug delivery device 9410 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9410 is shown as two separate components upper housing9412A and lower housing 9412B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe variable rate controlled delivery drive mechanism and/or drugdelivery device to each other. Alternatively, one or more components ofthe variable rate controlled delivery drive mechanism and/or drugdelivery device may be a unified component. For example, the upperhousing and lower housing may be separate components affixed together bya glue or adhesive, a screw fit connection, an interference fit, fusionjoining, welding, ultrasonic welding, and the like; or the upper housingand lower housing may be a single unified component. Such standardcomponents and functional variations would be appreciated by one havingordinary skill in the art and are, accordingly, within the breadth andscope of the present disclosure.

It will be appreciated from the above description that the drivemechanisms and drug delivery devices disclosed herein provide anefficient and easily-operated system for automated drug delivery from adrug container. The novel embodiments described herein provide drivemechanisms for the controlled delivery of drug substances and drugdelivery pumps which incorporate such drive mechanisms. The drivemechanisms of the present disclosure control the rate of drug deliveryby metering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container and, thus, are capable of delivering drug substancesat desired rates and/or delivery profiles. Additionally, the drivemechanisms of the present disclosure provide integrated statusindication features which provide feedback to the user before, during,and after drug delivery. For example, the user may be provided aninitial feedback to identify that the system is operational and readyfor drug delivery. Upon activation, the system may then provide one ormore drug delivery status indications to the user. At completion of drugdelivery, the drive mechanism and drug delivery device may provide anend-of-dose indication. The novel drive mechanisms of the presentdisclosure may be directly or indirectly activated by the user.Furthermore, the novel configurations of the controlled delivery drivemechanism and drug delivery devices of the present disclosure maintainthe sterility of the fluid pathway during storage, transportation, andthrough operation of the device. Because the path that the drug fluidtravels within the device is entirely maintained in a sterile condition,only these components need be sterilized during the manufacturingprocess. Such components include the drug container of the drivemechanism, the fluid pathway connector, the sterile fluid conduit, andthe insertion mechanism. In at least one embodiment of the presentdisclosure, the power and control system, the assembly platform, thecontrol arm, the activation mechanism, the housing, and other componentsof the drug delivery device do not need to be sterilized. This greatlyimproves the manufacturability of the device and reduces associatedassembly costs. Accordingly, the devices of the present disclosure donot require terminal sterilization upon completion of assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theforce applied by a torsional power spring acting upon (directly orindirectly) a piston within a drug container to force fluid drug flowthrough the drug container, the fluid pathway connector, a sterile fluidconduit, and the insertion mechanism for delivery of the fluid drug tothe body of a user, wherein a regulating mechanism acting to restrainthe force applied by the power spring is utilized to meter the freeaxial translation of the piston. The method of operation of theinsertion mechanism and the drug delivery device may be betterappreciated with reference to FIGS. 96A-96C and FIGS. 97A-97C, asdescribed above.

XIV. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 69A-73D, 80A-85C, 86A-91, and 92-99 may be configured toincorporate the embodiments of the drive mechanism described below inconnection with FIGS. 100A-109B. The embodiments of the drive mechanismdescribed below in connection with FIGS. 100A-109B may be used toreplace, in its entirety or partially, the above-described drivemechanism 100, 6100, 8100, 9010, 9210, 9310, or 9410, or any other drivemechanism described herein, where appropriate.

The present disclosure provides drive mechanisms for the variable ratecontrolled delivery of drug substances, drug delivery pumps withvariable rate drive mechanisms, the methods of operating such devices,and the methods of assembling such devices. Notably, the drivemechanisms of the present disclosure control the rate of drug deliveryby metering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container. The novel embodiments of the present disclosurethus are capable of delivering drug substances at variable rates. Thevariable rate drive mechanisms of the present disclosure may bepre-configurable or dynamically configurable, such as by control by thepower and control system, to meet desired delivery rates or profiles, asexplained in detail below. Additionally, the drive mechanisms of thepresent disclosure provide integrated status indication features whichprovide feedback to the user before, during, and after drug delivery.For example, the user may be provided an initial feedback to identifythat the system is operational and ready for drug delivery. Uponactivation, the system may then provide one or more drug delivery statusindications to the user. At completion of drug delivery, the drivemechanism and drug delivery device may provide an end-of-doseindication. Because the end-of-dose indication is related to thephysical end of axial translation of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the novel devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a variable ratecontrolled delivery drive mechanism which includes a drive mechanismhousing, at least partially within which initially resides a biasingmember positioned in an initially energized state within an inner cavityof a piston. The drive mechanism may further includes a gear drivehaving a gear and a substantially axial internal pass-through; a firstscrew which at least partially resides within the axial internalpass-through, said first screw also having a substantially axialpass-through and an external first pitch wherein the external firstpitch is configured to engage a first nut which also resides within theinternal pass-through of the gear drive; a second nut configured toengage a second screw having an external second pitch, said second nutpositioned within an axial post of a piston, said axial post and secondnut positioned to reside at least partially within the axialpass-through of the first screw. The piston has an interface surfaceadjacent to a plunger seal and is configured to axially translate theplunger seal, by force asserted upon it from the biasing member, from afirst position to a second position within a drug container for drugdelivery. The biasing member is member is metered or otherwiserestrained from free expansion from its energized state. The first nutmay be rotationally constrained (i.e. keyed) to the gear drive, whilethe second nut is rotationally constrained to the piston.

In another embodiment, the present disclosure provides a variable ratecontrolled delivery drive mechanism having a drive mechanism housing, atleast partially within which initially resides a biasing memberpositioned in an initially energized state within an inner cavity of apiston. A gear may be connected to the proximal end of a drive screwhaving an external pitch configured to engage a nut. The nut may berotationally constrained (i.e., keyed) to the piston. The piston has aninterface surface adjacent to a plunger seal and is configured toaxially translate the plunger seal, by force asserted upon it from thebiasing member, from a first position to a second position within a drugcontainer for drug delivery. The biasing member is metered or otherwiserestrained from free expansion from its energized state.

In at least one embodiment, the drive mechanism may further include agear assembly mechanism having a motor, the gear assembly mechanismconfigured to engage a gear to meter the free expansion of the biasingmember from its energized state. The gear assembly mechanism having amotor may further include a pinion extending from motor; one or morecompound gears each having a first gear and a second gear; and a triggergear; wherein the pinion contacts the one or more compound gears whichcontacts the trigger gear, and the trigger gear contacts a gear to relaymotion to the drive mechanism. The metering of the biasing member by themotor controls the rate or profile of drug delivery to a user.

In a further embodiment, the drive mechanism includes a status readerconfigured to read or recognize one or more corresponding statustriggers, wherein, during operation of the drive mechanism, interactionbetween the status reader and the status triggers transmits a signal toa power and control system to provide feedback to a user. The statusreader may be, for example, an optical status reader and thecorresponding status triggers are gear teeth of the trigger gear, amechanical status reader and the corresponding status triggers are gearteeth of the trigger gear, a mechanical status reader and thecorresponding status triggers are external features of the piston and/orsleeve an optional sleeve, or an optical status reader and thecorresponding status triggers are external features of the piston and/oran optional sleeve. The function of the gear assembly mechanism having amotor may be pre-programmed or dynamically controlled by a power andcontrol system to meet a desired drug delivery rate or profile.

In yet another embodiment, the present disclosure provides a drugdelivery pump with a variable rate controlled delivery mechanism. Thedrive mechanism may be as described above. In at least one embodiment,the drug delivery device may further include a gear assembly mechanismhaving a motor, the gear assembly mechanism configured to engage a gearto meter the free expansion of the biasing member from its energizedstate. The gear assembly mechanism having a motor may further include apinion extending from motor; one or more compound gears each having afirst gear and a second gear; and a trigger gear; wherein the pinioncontacts the one or more compound gears which contacts the trigger gear,and the trigger gear contacts a gear to relay motion to the drivemechanism. The metering of the biasing member by the motor controls therate or profile of drug delivery to a user.

In a further embodiment, the drug delivery device includes a statusreader configured to read or recognize one or more corresponding statustriggers, wherein, during operation of the drive mechanism, interactionbetween the status reader and the status triggers transmits a signal toa power and control system to provide feedback to a user. The statusreader may be, for example, an optical status reader and thecorresponding status triggers are gear teeth of the trigger gear, amechanical status reader and the corresponding status triggers are gearteeth of the trigger gear, a mechanical status reader and thecorresponding status triggers are external features of the piston and/orsleeve an optional sleeve, or an optical status reader and thecorresponding status triggers are external features of the piston and/oran optional sleeve. The function of the gear assembly mechanism having amotor may be pre-programmed or dynamically controlled by a power andcontrol system to meet a desired drug delivery rate or profile.

The present disclosure provides variable rate drive mechanisms for thecontrolled delivery of drug substances and drug delivery pumps whichincorporate such variable rate drive mechanisms. The variable rate drivemechanisms of the present disclosure control the rate of drug deliveryby metering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container and, thus, are capable of delivering drug substancesat variable rates and/or delivery profiles. Additionally, the variablerate drive mechanisms of the present disclosure provide integratedstatus indication features which provide feedback to the user before,during, and after drug delivery. For example, the user may be providedan initial feedback to identify that the system is operational and readyfor drug delivery. Upon activation, the system may then provide one ormore drug delivery status indications to the user. At completion of drugdelivery, the variable rate drive mechanism and drug delivery device mayprovide an end-of-dose indication.

The novel devices of the present disclosure provide variable ratecontrolled delivery drive mechanisms with integrated status indicationand drug delivery pumps which incorporate such drive mechanisms. Suchdevices are safe and easy to use, and are aesthetically andergonomically appealing for self-administering patients. The devicesdescribed herein incorporate features which make activation, operation,and lock-out of the device simple for even untrained users. The noveldevices of the present disclosure provide these desirable featureswithout any of the problems associated with known prior art devices.Certain non-limiting embodiments of the novel drug delivery pumps, drivemechanisms, and their respective components are described further hereinwith reference to the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.100A-100C show an exemplary drug delivery device or drug delivery deviceaccording to at least one embodiment of the present disclosure. The drugdelivery device may be utilized to administer delivery of a drugtreatment into a body of a user. As shown in FIGS. 100A-100C, the drugdelivery device 9510 includes a pump housing 9512. Pump housing 9512 mayinclude one or more housing subcomponents which are fixedly engageableto facilitate easier manufacturing, assembly, and operation of the drugdelivery device. For example, drug delivery device 9510 includes a pumphousing 9512 which includes an upper housing 9512A and a lower housing9512B. The drug delivery device may further include an activationmechanism 9514, a status indicator 9516, and a window 9518. Window 9518may be any translucent or transmissive surface through which theoperation of the drug delivery device may be viewed. As shown in FIG.100B, drug delivery device further includes assembly platform 9520,sterile fluid conduit 9530, drive mechanism 95100 having drug container9550, insertion mechanism 95200, fluid pathway connector 95300, andpower and control system 95400. One or more of the components of suchdrug delivery devices may be modular in that they may be, for example,pre-assembled as separate components and configured into position ontothe assembly platform 9520 of the drug delivery device 9510 duringmanufacturing.

The pump housing 9512 contains all of the device components and providesa means of removably attaching the device 9510 to the skin of the user.The pump housing 9512 also provides protection to the interiorcomponents of the device 9510 against environmental influences. The pumphousing 9512 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9512 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9512 may include certaincomponents, such as status indicator 9516 and window 9518, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9510 provides anactivation mechanism 9514 that is displaced by the user to trigger thestart command to the power and control system 95400. In a preferredembodiment, the activation mechanism is a start button 9514 that islocated through the pump housing 9512, such as through an aperturebetween upper housing 9512A and lower housing 9512B, and which contactsa control arm 9540 of the power and control system 95400. In at leastone embodiment, the start button 9514 may be a push button, and in otherembodiments, may be an on/off switch, a toggle, or any similaractivation feature known in the art. The pump housing 9512 also providesa status indicator 9516 and a window 9518. In other embodiments, one ormore of the activation mechanism 9514, the status indicator 16, thewindow 9518, and combinations thereof may be provided on the upperhousing 9512A or the lower housing 9512B such as, for example, on a sidevisible to the user when the drug delivery device 9510 is placed on thebody of the user. Housing 9512 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device is configured such that, upon activation by a userby depression of the activation mechanism, the drug delivery device isinitiated to: insert a fluid pathway into the user; enable, connect, oropen necessary connections between a drug container, a fluid pathway,and a sterile fluid conduit; and force drug fluid stored in the drugcontainer through the fluid pathway and fluid conduit for delivery intoa user. One or more optional safety mechanisms may be utilized, forexample, to prevent premature activation of the drug delivery device.For example, an optional on-body sensor 9524 (shown in FIG. 100C) may beprovided in one embodiment as a safety feature to ensure that the powerand control system 95400, or the activation mechanism, cannot be engagedunless the drug delivery device 9510 is in contact with the body of theuser. In one such embodiment, the on-body sensor 9524 is located on thebottom of lower housing 9512B where it may come in contact with theuser's body. Upon displacement of the on-body sensor 9524, depression ofthe activation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor 9524 is a mechanical safety mechanism,such as for example a mechanical lock out, that prevents triggering ofthe drug delivery device 9510 by the activation mechanism 9514. Inanother embodiment, the on-body sensor may be an electro-mechanicalsensor such as a mechanical lock out that sends a signal to the powerand control system 95400 to permit activation. In still otherembodiments, the on-body sensor can be electrically based such as, forexample, a capacitive- or impedance-based sensor which must detecttissue before permitting activation of the power and control system95400. These concepts are not mutually exclusive and one or morecombinations may be utilized within the breadth of the presentdisclosure to prevent, for example, premature activation of the drugdelivery device. In a preferred embodiment, the drug delivery device9510 utilizes one or more mechanical on-body sensors. Additionalintegrated safety mechanisms are described herein with reference toother components of the novel drug delivery devices.

XIV.A. Power and Control System

The power and control system 95400 includes a power source, whichprovides the energy for various electrical components within the drugdelivery device, one or more feedback mechanisms, a microcontroller, acircuit board, one or more conductive pads, and one or moreinterconnects. Other components commonly used in such electrical systemsmay also be included, as would be appreciated by one having ordinaryskill in the art. The one or more feedback mechanisms may include, forexample, audible alarms such as piezo alarms and/or light indicatorssuch as light emitting diodes (LEDs). The microcontroller may be, forexample, a microprocessor. The power and control system 95400 controlsseveral device interactions with the user and interfaces with the drivemechanism 95100. In one embodiment, the power and control system 95400interfaces with the control arm 9540 to identify when the on-body sensor9524 and/or the activation mechanism 9514 have been activated. The powerand control system 95400 may also interface with the status indicator9516 of the pump housing 9512, which may be a transmissive ortranslucent material which permits light transfer, to provide visualfeedback to the user. The power and control system 95400 interfaces withthe drive mechanism 95100 through one or more interconnects to relaystatus indication, such as activation, drug delivery, and end-of-dose,to the user. Such status indication may be presented to the user viaauditory tones, such as through the audible alarms, and/or via visualindicators, such as through the LEDs. In a preferred embodiment, thecontrol interfaces between the power and control system and the othercomponents of the drug delivery device are not engaged or connecteduntil activation by the user. This is a desirable safety feature thatprevents accidental operation of the drug delivery device and mayadditionally maintain the energy contained in the power source duringstorage, transportation, and the like.

The power and control system 95400 may be configured to provide a numberof different status indicators to the user. For example, the power andcontrol system 95400 may be configured such that after the on-bodysensor and/or trigger mechanism have been pressed, the power and controlsystem 95400 provides a ready-to-start status signal via the statusindicator 9516 if device start-up checks provide no errors. Afterproviding the ready-to-start status signal and, in an embodiment withthe optional on-body sensor, if the on-body sensor remains in contactwith the body of the user, the power and control system 95400 will powerthe drive mechanism 95100 to begin delivery of the drug treatmentthrough the fluid pathway connector 95300 and sterile fluid conduit9530. In a preferred embodiment of the present disclosure, the insertionmechanism 95200 and the fluid pathway connector 95300 may be caused toactivate directly by user operation of the activation mechanism 9514.During the drug delivery process, the power and control system 95400 isconfigured to provide a dispensing status signal via the statusindicator 9516. After the drug has been administered into the body ofthe user and after the end of any additional dwell time, to ensure thatsubstantially the entire dose has been delivered to the user, the powerand control system 95400 may provide an okay-to-remove status signal viathe status indicator 9516. This may be independently verified by theuser by viewing the drive mechanism and drug dose delivery through thewindow 18 of the pump housing 9512. Additionally, the power and controlsystem 95400 may be configured to provide one or more alert signals viathe status indicator 9516, such as for example alerts indicative offault or operation failure situations.

The power and control system 95400 may additionally be configured toaccept various inputs from the user to dynamically control the drivemechanisms 95100 to meet a desired drug delivery rate or profile. Forexample, the power and control system 95400 may receive inputs, such asfrom partial or full activation, depression, and/or release of theactivation mechanism 9514, to set, initiate, stop, or otherwise adjustthe control of the drive mechanism 95100 via the power and controlsystem 95400 to meet the desired drug delivery rate or profile.Similarly, the power and control system 95400 may be configured toreceive such inputs to adjust the drug dose volume; to prime the drivemechanism, fluid pathway connector, and fluid conduit; and/or to start,stop, or pause operation of the drive mechanism 95100. Such inputs maybe received by the user directly acting on the drug delivery device9510, such as by use of the activation mechanism 9514 or a differentcontrol interface, or the system 95400 may be configured to receive suchinputs from a remote device. Additionally or alternatively, such inputsmay be pre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism 9514 of the drugdelivery device 9510 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

XIV.B. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9510, the fluid pathway connector 95300 isenabled to connect the sterile fluid conduit 9530 to the drug containerof the drive mechanism 95100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 95100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user.

In at least one embodiment of the present disclosure, the piercingmember of the fluid pathway connector is caused to penetrate thepierceable seal of the drug container of the drive mechanism by directaction of the user, such as by depression of the activation mechanism bythe user. For example, the activation mechanism itself may bear on thefluid pathway connector such that displacement of the activationmechanism from its original position also causes displacement of thefluid pathway connector. In one such embodiment, the fluid pathwayconnector may be substantially similar to that described inInternational Patent Application No. PCT/US2012/054861, which isincluded by reference herein in its entirety for all purposes. Accordingto such an embodiment, the connection is enabled by the user depressingthe activation mechanism and, thereby, driving the piercing memberthrough the pierceable seal, because this prevents fluid flow from thedrug container until desired by the user. In such an embodiment, acompressible sterile sleeve may be fixedly attached between the cap ofthe drug container and the connection hub of the fluid pathwayconnector. The piercing member may reside within the sterile sleeveuntil a connection between the fluid connection pathway and the drugcontainer is desired. The sterile sleeve may be sterilized to ensure thesterility of the piercing member and the fluid pathway prior toactivation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Application No.PCT/US2013/030478, for example, which is included by reference herein inits entirety for all purposes. According to such an embodiment, a drugcontainer may have a drug chamber within a barrel between a pierceableseal and a plunger seal. A drug fluid is contained in the drug chamber.Upon activation of the device by the user, a drive mechanism asserts aforce on a plunger seal contained in the drug container. As the plungerseal asserts a force on the drug fluid and any air/gas gap or bubble, acombination of pneumatic and hydraulic pressure builds by compression ofthe air/gas and drug fluid and the force is relayed to the slidingpierceable seal. The sliding pierceable seal is caused to slide towardsthe cap, causing it to be pierced by the piercing member retained withinthe integrated sterile fluid pathway connector. Accordingly, theintegrated sterile fluid pathway connector is connected (i.e., the fluidpathway is opened) by the combination pneumatic/hydraulic force of theair/gas and drug fluid within the drug chamber created by activation ofa drive mechanism. Once the integrated sterile fluid pathway connectoris connected or opened, drug fluid is permitted to flow from the drugcontainer, through the integrated sterile fluid pathway connector,sterile fluid conduit, and insertion mechanism, and into the body of theuser for drug delivery. In at least one embodiment, the fluid flowsthrough only a manifold and a cannula and/or needle of the insertionmechanism, thereby maintaining the sterility of the fluid pathway beforeand during drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 95300 and the sterile fluid conduit 9530 are providedhereinafter in later sections in reference to other embodiments.

XIV.C. Insertion Mechanism

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure.

In at least one embodiment, the insertion mechanism 95200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 100B and FIG. 100C). The connection of the base to theassembly platform 9520 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9510. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 30 to permitfluid flow through the manifold, cannula, and into the body of the userduring drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9527 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane 95254 (shown in FIG. 100C).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. As shown in FIG. 100B, thelockout pin(s) 95208 may be directly displaced by user depression of theactivation mechanism 9514. As the user disengages any safety mechanisms,such as an optional on-body sensor 9524 (shown in FIG. 100C), theactivation mechanism 9514 may be depressed to initiate the drug deliverydevice. Depression of the activation mechanism 9514 may directly causetranslation or displacement of control arm 9540 and directly orindirectly cause displacement of lockout pin(s) 95208 from their initialposition within locking windows 95202A of insertion mechanism housing95202. Displacement of the lockout pin(s) 95208 permits insertionbiasing member to decompress from its initial compressed, energizedstate. This decompression of the insertion biasing member drives theneedle and the cannula into the body of the user. At the end of theinsertion stage, the refraction biasing member is permitted to expand inthe proximal direction from its initial energized state. This axialexpansion in the proximal direction of the refraction biasing memberrefracts the needle, while maintaining the cannula in fluidcommunication with the body of the user. Accordingly, the insertionmechanism may be used to insert a needle and cannula into the user and,subsequently, retract the needle while retaining the cannula in positionfor drug delivery to the body of the user.

XIV.D. Drive Mechanism

With reference to the embodiments shown in FIGS. 101 and 102, drivemechanism 95100 includes a drive housing 95130, and a drug container9550 having a cap 9552, a pierceable seal 9556, a barrel 9558, and aplunger seal 9560. A drug chamber 9521, located within the barrel 9558between the pierceable seal and the plunger seal 9560, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. The seals described hereinmay be comprised of a number of materials but are, in a preferredembodiment, comprised of one or more elastomers or rubbers. The drivemechanism may further include a connection mount 9554 to guide theinsertion of the piercing member of the fluid pathway connector into thebarrel 9558 of the drug container 9550. The drive mechanism 95100 mayfurther contain one or more drive biasing members, one or more releasemechanisms, and one or more guides, as are described further herein. Thecomponents of the drive mechanism function to force a fluid from thedrug container out through the pierceable seal, or preferably throughthe piercing member of the fluid pathway connector, for delivery throughthe fluid pathway connector, sterile fluid conduit, and insertionmechanism into the body of the user.

In one particular embodiment, the drive mechanism 95100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. The fluid pathway connector may beconnected through the pierceable seal prior to, concurrently with, orafter activation of the drive mechanism to permit fluid flow from thedrug container, through the fluid pathway connector, sterile fluidconduit, and insertion mechanism, and into the body of the user for drugdelivery. In at least one embodiment, the fluid flows through only amanifold and a cannula of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detailhereinafter.

Referring now to the embodiment of the drive mechanism shown in FIG. 101and FIG. 95102, the drive mechanism 95100 includes a drug container 9550having a cap 9552, a pierceable seal 9556, a barrel 9558, and a plungerseal 9560, and optionally a connection mount 9554. The drug container9550 is mounted to a distal end of a drive housing 130. Compressedwithin the drive housing 95130, between the drug container 9550 and theproximal end of the housing 95130, are a drive biasing member 95122 anda piston 95110, wherein the drive biasing member 95122 is configured tobear upon an interface surface 95110C of the piston 95110, as describedfurther herein. Optionally, a cover sleeve 95140 may be utilized toengage the piston 95110 and cover the drive biasing member 95122 to hidethe biasing member 95122 from user view upon expansion from its initialenergized state. The cover sleeve 95140 may be configured to engage andslide upon the piston 95110, between the piston 95110 and the distal endof the drive mechanism housing 95130 to hide the biasing member 95122from user view upon expansion from its initial energized state.

As shown in FIG. 102, the variable rate controlled delivery drivemechanism 95100 of the present disclosure may utilize a telescopingdrive assembly which incorporates a gear drive 95120 having a gear 95520and a substantially axial internal pass-through 95120A, within which atleast partially resides a first screw 95124 having a substantially axialpass-through 95124A and an external first pitch 95124B. The externalfirst pitch 95124B is configured to engage and rotationally translateupon or within a first nut 95126 which also resides within the internalpass-through 95120A of the gear drive 95120 (such as at the distal endof the internal pass-through 95120A). Similarly, a second nut 95128resides within the axial pass-through 95124A of the first screw 95124and is configured to engage and rotationally translate a second screw95132 having an external second pitch 95132B. More accurately, thesecond nut 95128 resides within an axial post 95110B of the piston95110, which itself resides at least partially within the axialpass-through 124A of the first screw 95124. The second nut 95128 isconfigured to engage and rotationally translate upon or around thesecond screw 95132 having the external second pitch 95132B. Theseaspects are more clearly visible with reference to FIGS. 103A-103C andFIGS. 104A-104C. Because of this configuration of components, andbecause the axial rotation of the gear drive 95120 indirectly causesaxial translation of the piston 95110, the variable rate controlleddelivery drive mechanism shown in FIGS. 101, 102, 103A-103C and104A-104C is referred to as a “telescoping” drive mechanism. The geardrive 95120, notably, does not drive the delivery but only controls thedelivery motion. The gear drive 95120 controls the motion of the piston95110 and plunger seal 9560, but does not apply the force necessary fordrug delivery. Instead, the gear drive 95120 merely meters or permitstranslation of the piston 95110 and plunger seal 9560 which are beingdriven to axially translate by the biasing member 95122. Because theaxial translation of the piston 95110 and plunger seal 9560 are drivenby biasing member 95122, and the gear drive 95120 is merely metering orpermitting axial translation, the force or power needed to meter theaxial translation by the gear drive 95120 is much smaller than thatwhich would be required if the gear drive did drive the delivery.Accordingly, a smaller motor may be utilized by the embodiments of thepresent disclosure. The motor 95530 may, accordingly, be selected from avariety of electromechanical sources capable of incremental motion, suchas brushed DC motors, EC motors, stepper motors, solenoids, or othertechnologies that can produce controlled motion. In at least oneembodiment, the motor 95530 is most preferably a stepper motor.

Alternatively, a non-telescoping drive mechanism, as shown in FIGS. 105,106, 107A-107C and 108A-108C may be utilized within the embodiments ofthe present disclosure. Referring now to the embodiment of the drivemechanism shown in FIG. 105 and FIG. 106, the drive mechanism 951100includes a drug container 951050 having a cap 951052, a pierceable seal951056, a barrel 951058, and a plunger seal 951060, and optionally aconnection mount 951054. The drug container 951050 is mounted to adistal end of a drive housing 951130. Compressed within the drivehousing 951130, between the drug container 951050 and the proximal endof the housing 951130, are a drive biasing member 951122 and a piston951110, wherein the drive biasing member 951122 is configured to bearupon an interface surface 951110C of the piston 951110, as describedfurther herein. As shown in FIG. 106, the variable rate controlleddelivery drive mechanism 951100 of the present disclosure may utilize anon-telescoping drive assembly which incorporates a gear 951520connected to the proximal end of a drive screw 951124 having an externalpitch 951124B. The external pitch 951124B is configured to engage androtationally translate upon or within a nut 951126. As the gear 951520and drive screw 951124 are axially rotated, the threaded engagementbetween the drive screw 951124 and the nut 951126 permits axialtranslation of the piston 951110 by the biasing member 951122. Theseaspects are more clearly visible with reference to FIGS. 107A-107C andFIGS. 108A-108C. Because the axial rotation of the drive screw 951124directly causes axial translation of the piston 951110, such embodimentsof the present disclosure are referred to herein as “non-telescoping”.As stated above with regard to the first embodiment, the drive screw951124, notably, does not drive the delivery but only controls thedelivery motion. The drive screw 951124 controls the motion of thepiston 951110 and plunger seal 951060, but does not apply the forcenecessary for drug delivery. Instead, the drive screw 951124 merelymeters or permits translation of the piston 951110 and plunger seal951060 which are being driven to axially translate by the biasing member951122. Because the axial translation of the piston 951110 and plungerseal 951060 are driven by biasing member 951122, and the drive screw951124 is merely metering or permitting axial translation, the force orpower needed to meter the axial translation by the drive screw 951124 ismuch smaller than that which would be required if the drive screw diddrive the delivery. Accordingly, a smaller motor may be utilized by theembodiments of the present disclosure. The motor 951530 may,accordingly, be selected from a variety of electromechanical sourcescapable of incremental motion, such as brushed DC motors, EC motors,stepper motors, solenoids, or other technologies that can producecontrolled motion. In at least one embodiment, the motor 951530 is mostpreferably a stepper motor.

FIGS. 103A-103C and FIGS. 104A-104C show the progression of the variablerate controlled delivery drive mechanism, according to the embodimentshown in FIGS. 101-102 having a telescoping drive mechanismconfiguration, as it progresses through activation, controlled deliveryof a drug substance, and completion of drug delivery. As shown, a geartransmission assembly 95500 having a motor 95530 may be utilized tometer or otherwise prevent free axial translation of the biasing member95122 used to push a plunger seal 9560 for the delivery of a drugsubstance out of drug chamber 9521. The gear transmission assembly 95500is further detailed below with reference to FIGS. 109A-109B. Uponactuation of the variable rate controlled delivery drive mechanism 95100by the user, such as by activation of the power and control system, themotor 95530 is caused to rotate the components of the gear transmissionassembly 95500 to correspondingly rotate gear 95520. Substantiallysimultaneously or in advance of such activation of the motor 95530, thebiasing member 95122 is unlocked or otherwise permitted to release fromits initial energized state. The biasing member 95122 is positionedwithin the drive mechanism housing 95130 and held in an initialenergized state between the drive mechanism housing 95130 and theinterior of the interface surface 95110C of piston 95110. Upon suchunlocking or release the biasing member 95122 will act upon and push thepiston 95110 (and the plunger seal 9560 located substantially adjacentthe piston 95110 on the other side of the interface surface 95110C) todrive the plunger seal 60 for drug delivery, if the biasing member 95122is unrestrained or not otherwise metered. The novel variable ratecontrolled delivery drive mechanisms of the present disclosure areconfigured to provide such restraint or metering on the expansion of thebiasing member 95122. Depending on a desired drug delivery rate orprofile, as may be pre-programmed or dynamically controlled by the powerand control system, the motor 95530 of the gear assembly mechanism 95500may function to incrementally permit axial expansion of the biasingmember 95122 and, thus, axial translation of the piston 95110 andplunger seal 9560.

As the components of the gear assembly mechanism 95500 are rotated byfunction of the motor 530 and corresponding gear interactions, gear95520 is caused to rotate. A gear drive 95120 is connected to, or formedas part of, gear 95520 such that axial rotation of the gear 9520 causesaxial rotation of the gear drive 95120. Gear drive 95520 has an internalpass-through 95120 that is substantially axial, within which at leastpartially resides a first screw 95124 having a substantially axialpass-through 95124A and an external first pitch 95124B. The externalfirst pitch 95124B is configured to engage and rotationally translateupon or within a first nut 95126 which also resides within the internalpass-through 95120A of the gear drive 95120 (such as at the distal endof the internal pass-through 95120A). The first nut 95126 isrotationally keyed (i.e., constrained) or otherwise held in position(but permitted to axially translate) within the internal pass-through95120A of gear drive 95120. As stated above, upon activation of thedrive mechanism by the user, biasing member 95122 will apply a force topiston 95110 which is metered or restrained by the drive mechanism. Asthe gear drive 95120 is caused to axially rotate, the keyed engagementof the first nut 95126 with the gear drive 95120 and the movableengagement between corresponding gear teeth of the first screw 95124 (atthe external first pitch 95124B) with the first nut 95126 permits axialtranslation of the first screw 95124. Similarly, a second nut 95128resides within the axial pass-through 95124A of the first screw 95124and is configured to engage and rotationally translate a second screw95132 having an external second pitch 95132B. More accurately, thesecond nut 95128 resides within an axial post 95110B of the piston95110, which itself resides at least partially within the axialpass-through 95124A of the first screw 95124. The second nut 95128 isconfigured to engage and rotationally translate upon or around thesecond screw 95132 having the external second pitch 95132B.

Accordingly, axial rotation (and translation) of the first screw 95124permits axial rotation and axial translation of the second screw 95132.Accordingly, axial rotation of the gear 95520 and gear drive 95120causes axial rotation and axial translation of the first screw 95124.This is shown in the transition from FIG. 103A to FIG. 103B to FIG.103C, and in the transition from FIG. 104A to FIG. 104B to FIG. 104C.Because the biasing member 95122 is applying a force to piston 95110,the metering by the components of the drive mechanism permits thebiasing member 95122 to axially translate the piston 95110 and plungerseal 9560 at variable rates or profiles for controlled drug delivery.

The variable rate controlled delivery drive mechanisms of the presentdisclosure can, of course, be configured such that both the first screwand second screw are caused to axially translate simultaneously, such asby manipulating the pitch ratio of the external first pitch 95124B tothe external second pitch 95132B and their respective interactions withfirst nut 95126 and second nut 95128. As stated above, the gear drive95120 notably does not drive the delivery but only controls the deliverymotion. The gear drive 95120 controls the motion of the piston 19510 andplunger seal 9560, but does not apply the force necessary for drugdelivery. Instead, the gear drive 95120 merely meters or permitstranslation of the piston 95110 and plunger seal 9560 which are beingdriven to axially translate by the biasing member 95122. Because theaxial translation of the piston 95110 and plunger seal 9560 are drivenby biasing member 95122, and the gear drive 95120 is merely metering orpermitting axial translation, the force or power needed to meter theaxial translation by the gear drive 95120 is much smaller than thatwhich would be required if the gear drive did drive the delivery.Optionally, a cover sleeve 140 may be utilized to hide the visibility ofthe biasing member 95122 and other internal components from the user asthe piston 95110 is axially translated by the biasing member 95122. Thecover sleeve 95140 may also assist in maintaining a rotationally fixedrelationship between the non-rotating (relative to gear drive 95120)components of the drive mechanism, including for example the drivemechanism housing 95130 and the piston 95110. This rotational constraintpermits the screws and corresponding nuts to axially rotate, while thepiston is permitted to axially translate. The embodiments shown in thesefigures utilize a telescoping drive mechanism configuration to obtaingreater available axial translation while maintaining a smallerarrangement or dimensional footprint when in the compressed position.

FIGS. 107A-107C and FIGS. 108A-108C show the progression of the variablerate controlled delivery drive mechanism, according to the embodimentshown in FIGS. 105-106 having a non-telescoping drive mechanismconfiguration, as it progresses through activation, controlled deliveryof a drug substance, and completion of drug delivery. As shown, a geartransmission assembly 951500 having a motor 951530 may be utilized tometer or otherwise prevent free axial translation of the biasing member951122 used to push a plunger seal 951060 for the delivery of a drugsubstance out of drug chamber 951021. The gear transmission assembly951500 is further detailed below with reference to FIGS. 109A-109B. Uponactuation of the variable rate controlled delivery drive mechanism951100 by the user, such as by activation of the power and controlsystem, the motor 95530 is caused to rotate the components of the geartransmission assembly 951500 to correspondingly rotate gear 951520.Substantially simultaneously or in advance of such activation of themotor 951530, the biasing member 951122 is unlocked or otherwisepermitted to release from its initial energized state. The biasingmember 951122 is positioned within the drive mechanism housing 951130and held in an initial energized state between the drive mechanismhousing 951130 and the interior of the interface surface 951110C ofpiston 951110. Upon such unlocking or release the biasing member 951122will act upon and push the piston 951110 (and the plunger seal 951060located substantially adjacent the piston 951110 on the other side ofthe interface surface 951110C) to drive the plunger seal 951060 for drugdelivery, if the biasing member 951122 is unrestrained or not otherwisemetered. The novel variable rate controlled delivery drive mechanisms ofthe present disclosure are configured to provide such restraint ormetering on the expansion of the biasing member 951122. Depending on adesired drug delivery rate or profile, as may be pre-programmed ordynamically controlled by the power and control system, the motor 951530of the gear assembly mechanism 951500 may function to incrementallypermit axial expansion of the biasing member 951122 and, thus, axialtranslation of the piston 951110 and plunger seal 951060.

As the components of the gear assembly mechanism 951500 are rotated byfunction of the motor 951530 and corresponding gear interactions, gear951520 is caused to rotate. A drive screw 951124 having an externalpitch 951124B is connected to, or formed as part of, gear 951520. Theexternal pitch 951124B is configured to engage and rotationallytranslate upon or within a nut 951126. As the gear 951520 and drivescrew 951124 are axially rotated, the threaded engagement andcorresponding interaction between the external pitch 951124B of thedrive screw 951124 and the nut 951126 permits axial translation of thepiston 951110 by the biasing member 951122. As stated above withreference to the telescoping embodiments of the present disclosure, thepiston 951110 of the non-telescoping embodiments is rotationally keyed(i.e., constrained) to the drive housing 951130, relative to the drivescrew 951124. Nut 951126 is likewise keyed to piston 951110, whichconfiguration allows for axial translation of the piston 951110. Becausethe axial rotation of the drive screw 951124 directly permits axialtranslation of the piston 951110, such embodiments of the presentdisclosure are referred to herein as “non-telescoping”. As stated abovewith regard to the first embodiment, the drive screw 951124, notably,does not drive the delivery but only controls the delivery motion. Thedrive screw 951124 controls the motion of the piston 951110 and plungerseal 951060, but does not apply the force necessary for drug delivery.Instead, the drive screw 951124 merely meters or permits translation ofthe piston 951110 and plunger seal 1060 which are being driven toaxially translate by the biasing member 951122. Optionally, a washer orbearing 951580 may be utilized to facilitate axial rotation of gear951520 within the drive mechanism housing 951130. Additionally, thedrive mechanisms described herein may include one or more compliancefeatures which enable additional axial translation of the plunger seal9560, 951060 to, for example, ensure that substantially the entire drugdose has been delivered to the user. For example, the plunger seal 9560,951060, itself, may have some compressibility permitting a compliancepush of drug fluid from the drug container.

The novel variable rate drive mechanisms of the present disclosure mayoptionally integrate status indication into the drug dose delivery. Byuse of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user. Additionally oralternatively, an electromechanical status switch and interconnectassembly may be utilized to contact, connect, or otherwise enable atransmission to the power and control system to signal end-of-dose tothe user. For example, the status switch may be located distal to thepierceable seal 9556 and the interconnect located proximal to theplunger seal 9560 such that, upon substantially complete axialtranslation (and the optional compliance push) of the plunger seal 9560within the barrel 9558, the status switch and interconnect coordinate toenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

FIGS. 109A and 109B shows an isometric view of certain components of avariable rate controlled delivery drive mechanism, according to at leastone embodiment of the present disclosure. While such components areshown with reference to the embodiment detailed in FIGS. 101, 102,103A-103C, and 104A-104C, the same or similar components may be utilizedwith the other embodiments of the present disclosure. In at least oneembodiment, the gear assembly mechanism 95500 of the variable rate drivemechanisms 95100 of the present disclosure utilizes a motor 95530 withpinion 95530A. The pinion 95530A contacts a first gear 95526B of a firstcompound gear 95526. A second gear 95526A of the first compound gear95526 contacts a first gear 95528B of a second compound gear 95528, anda second gear 95528A (not visible) of the second compound gear 95528contacts a trigger gear 95524. Trigger gear 95524 contacts gear 95520 torelay motion to the remainder of drive mechanism 95100. As the motor95530 acts upon the gear assembly mechanism 95500, the motion isconveyed by interfacing gear teeth of the pinion 95530A, first compoundgear 95526, second compound gear 95528, trigger gear 95524, and gear95520. As detailed above, such motion is utilized to permit, meter orotherwise restrain the axial translation of the piston 95110 by thebiasing member 95122, thereby driving the plunger seal for drugdelivery. As the trigger gear 95524 rotates, a status reader 95600 mayread or recognize one or more corresponding status triggers on thetrigger gear 95524 to provide incremental status indication before,during, and after operation of the variable rate controlled deliverydrive mechanism. While the drive mechanisms of the present disclosureare described with reference to the gear assembly mechanism shown inFIGS. 109A and 95109B, a range of gear assembly configurations with theappropriate gear reduction based on the load and motor chosen would beacceptable and capable of being employed within the embodiments of thepresent disclosure, as would readily be appreciated by an ordinarilyskilled artisan. Accordingly, the embodiments of the present disclosureare not limited to the specific gear assembly mechanism describedherein, which is provided as an exemplary embodiment of such mechanismsfor employment within controlled delivery drive mechanisms and drugdelivery pumps.

As described above, a number of status readers may be utilized withinthe embodiments of the present disclosure. For example, the drivemechanism shown in FIG. 109A may utilize a mechanical status reader95600 which is physically contacted by gear teeth of the trigger gear95524. As the status reader 95600 is contacted by the status trigger(s),which in this exemplary embodiment are the gear teeth of the triggergear 95524, the status reader 95600 measures the rotational position ofthe trigger gear 95524 and transmits a signal to the power and controlsystem for status indication to the user. Additionally or alternatively,as shown in FIG. 95109B, the drive mechanism may utilize an opticalstatus reader 951600. The optical status reader 951600 may be, forexample, a light beam that is capable of recognizing a motion andtransmitting a signal to the power and control system. For example, thedrive mechanism shown in FIG. 109B may utilize an optical status reader951600 that is configured to recognize motion of the gear teeth of thetrigger gear 95524. As would be appreciated by one having ordinary skillin the art, optical status readers and corresponding triggers,electromechanical status readers and corresponding triggers, and/ormechanical status readers and corresponding triggers may all be utilizedby the embodiments of the present disclosure to provide incrementalstatus indication to the user.

Returning now to the embodiments shown in FIGS. 101-102 and FIGS.105-106, a fluid, such as a drug fluid, may be contained within barrel9558, 951058, in a drug chamber 9521, 951021 between plunger seal 9560,951060 and pierceable seal 9556, 951056, for delivery to a user. Thepierceable seal is adjacent or retained at least partially within cap9552, 951052. Upon activation by the user, a fluid pathway connector maybe connected to the drug container through the pierceable seal. Asdescribed above, this fluid connection may be facilitated by a piercingmember of the fluid pathway connector which pierces the pierceable sealand completes the fluid pathway from the drug container, through thefluid pathway connector, the fluid conduit, the insertion mechanism, andthe cannula for delivery of the drug fluid to the body of the user.Initially, one or more locking mechanisms (not shown) may retain thebiasing member 95122, 951122 in an initial energized position withinpiston 95110, 951110. Directly or indirectly upon activation of thedevice by the user, the locking mechanism may be removed to permitoperation of the drive mechanism. The piston 95110, 951110 and biasingmember 95122, 951122 are both initially in a compressed, energized statebehind (i.e., proximal to) the plunger seal 9560, 951060. The biasingmember 95122, 951122 may be maintained in this state until activation ofthe device between internal features of drive housing 95130, 951130 andinterface surface 95110C, 951110C of piston 95110, 951110. As thelocking mechanism is removed or displaced, biasing member 95122, 951122is permitted to expand (i.e., decompress) axially in the distaldirection (i.e., in the direction of the hatched arrow). Such expansioncauses the biasing member 95122, 1122 to act upon and distally translateinterface surface 95110C, 951110C and piston 95110, 951110, therebydistally translating plunger seal 9560, 951060 to push drug fluid out ofthe drug chamber 9521, 951021 of barrel 9558, 951058. Distal translationof the piston 95110, 951110 and plunger seal 60, 1060 continues to forcefluid flow out from barrel 9558, 951058 through pierceable seal 56,1056. In at least one embodiment, an end-of-dose status indication maybe provided to the user once the status reader recognizes a statustrigger positioned on the trigger gear to substantially correspond withthe end of axial travel of the piston 95110, 951110 and plunger 9560,951060. The gear assembly mechanism 95500, 951500 and novel drivemechanisms 95100, 951100 of the present disclosure thus permit, meter,or otherwise restrain the free axial expansion of the biasing member95122, 951122 to control the rate or profile of drug delivery. The novelembodiments of the present disclosure also thus provide incrementalstatus indication to the user.

Assembly and/or manufacturing of variable rate controlled delivery drivemechanism 95100, 951100, drug delivery pump 9510, or any of theindividual components may utilize a number of known materials andmethodologies in the art. For example, a number of known cleaning fluidssuch as isopropyl alcohol and hexane may be used to clean the componentsand/or the devices. A number of known adhesives or glues may similarlybe employed in the manufacturing process. Additionally, knownsiliconization and/or lubrication fluids and processes may be employedduring the manufacture of the novel components and devices. Furthermore,known sterilization processes may be employed at one or more of themanufacturing or assembly stages to ensure the sterility of the finalproduct.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9550 may first be assembledand filled with a fluid for delivery to the user. The drug container9550 includes a cap 9552, a pierceable seal 9556, a barrel 9558, and aplunger seal 9560. The pierceable seal 9556 may be fixedly engagedbetween the cap 9552 and the barrel 9558, at a distal end of the barrel9558. The barrel 9558 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9560 from theproximal end of the barrel 9558. An optional connection mount 9554 maybe mounted to a distal end of the pierceable seal 9556. The connectionmount 9554 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9558 of the drug container 9550. Thedrug container 50 may then be mounted to a distal end of drive housing95130.

A drive biasing member 95122 may be inserted into a distal end of thedrive housing 95130. Optionally, a cover sleeve 95140 may be insertedinto a distal end of the drive housing 130 to substantially coverbiasing member 95122. A piston may be inserted into the distal end ofthe drive housing 95130 such that it resides at least partially withinan axial pass-through of the biasing member 95122 and the biasing member95122 is permitted to contact a piston interface surface 95110C ofpiston 110 at the distal end of the biasing member 95122. The piston 110and drive biasing member 95122, and optional cover sleeve 95140, may becompressed into drive housing 95130. Such assembly positions the drivebiasing member 95122 in an initial compressed, energized state andpreferably places a piston interface surface 95110C in contact with theproximal surface of the plunger seal 9560 within the proximal end ofbarrel 9558. The piston, piston biasing member, contact sleeve, andoptional components, may be compressed and locked into theready-to-actuate state within the drive housing 95130 prior toattachment or mounting of the drug container 9550. The drive screw951124, or combination of first screw 95124 and second screw 95132, andtheir corresponding engagement components may be pre-assembled,connected to the piston 95110, mounted into the drive mechanism housing95130 and connected to gear drive 95120 and gear 95520 (or alternativelyconnected to gear 951520) which is placed in position through theproximal end of the drive mechanism housing 95130 such that it extendsproximally therefrom to engage the gear assembly mechanism 95500, 951500for operation.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 100B.

Certain optional standard components or variations of drive mechanism95100, drive mechanism 951100, or drug delivery device 9510 arecontemplated while remaining within the breadth and scope of the presentdisclosure. For example, the embodiments may include one or morebatteries utilized to power the motor, drive mechanisms, and drugdelivery devices of the present disclosure. A range of batteries knownin the art may be utilized for this purpose. Additionally, upper orlower housings may optionally contain one or more transparent ortranslucent windows 9518, as shown in FIG. 100A, to enable the user toview the operation of the drug delivery device 9510 or verify that drugdose has completed. Similarly, the drug delivery device 9510 may containan adhesive patch 9526 and a patch liner 9528 on the bottom surface ofthe housing 9512. The adhesive patch 9526 may be utilized to adhere thedrug delivery device 9510 to the body of the user for delivery of thedrug dose. As would be readily understood by one having ordinary skillin the art, the adhesive patch 9526 may have an adhesive surface foradhesion of the drug delivery device to the body of the user. Theadhesive surface of the adhesive patch 9526 may initially be covered bya non-adhesive patch liner 9528, which is removed from the adhesivepatch 9526 prior to placement of the drug delivery device 9510 incontact with the body of the user. Removal of the patch liner 9528 mayfurther remove the sealing membrane 95254 of the insertion mechanism95200, opening the insertion mechanism to the body of the user for drugdelivery (as shown in FIG. 100C).

Similarly, one or more of the components of variable rate controlleddelivery drive mechanism 95100, drive mechanism 951100, and drugdelivery device 9510 may be modified while remaining functionally withinthe breadth and scope of the present disclosure. For example, asdescribed above, while the housing of drug delivery device 9510 is shownas two separate components upper housing 9512A and lower housing 9512B,these components may be a single unified component. As discussed above,a glue, adhesive, or other known materials or methods may be utilized toaffix one or more components of the variable rate controlled deliverydrive mechanism and/or drug delivery device to each other.Alternatively, one or more components of the variable rate controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the variable ratedrive mechanisms and drug delivery devices disclosed herein provide anefficient and easily-operated system for automated drug delivery from adrug container. The novel embodiments described herein provide drivemechanisms for the controlled delivery of drug substances and drugdelivery pumps which incorporate such variable rate drive mechanisms.The drive mechanisms of the present disclosure control the rate of drugdelivery by metering, providing resistance, or otherwise preventing freeaxial translation of the plunger seal utilized to force a drug substanceout of a drug container and, thus, are capable of delivering drugsubstances at variable rates and/or delivery profiles. Additionally, thedrive mechanisms of the present disclosure provide integrated statusindication features which provide feedback to the user before, during,and after drug delivery. For example, the user may be provided aninitial feedback to identify that the system is operational and readyfor drug delivery. Upon activation, the system may then provide one ormore drug delivery status indications to the user. At completion of drugdelivery, the drive mechanism and drug delivery device may provide anend-of-dose indication. The novel variable rate drive mechanisms of thepresent disclosure may be directly or indirectly activated by the user.Furthermore, the novel configurations of the variable rate controlleddelivery drive mechanism and drug delivery devices of the presentdisclosure maintain the sterility of the fluid pathway during storage,transportation, and through operation of the device. Because the paththat the drug fluid travels within the device is entirely maintained ina sterile condition, only these components need be sterilized during themanufacturing process. Such components include the drug container of thedrive mechanism, the fluid pathway connector, the sterile fluid conduit,and the insertion mechanism. In at least one embodiment of the presentdisclosure, the power and control system, the assembly platform, thecontrol arm, the activation mechanism, the housing, and other componentsof the drug delivery device do not need to be sterilized. This greatlyimproves the manufacturability of the device and reduces associatedassembly costs. Accordingly, the devices of the present disclosure donot require terminal sterilization upon completion of assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the variable rate controlled delivery drive mechanism and drugcontainer, either separately or as a combined component, to an assemblyplatform or housing of the drug delivery device. The method ofmanufacturing further includes attachment of the fluid pathwayconnector, drug container, and insertion mechanism to the assemblyplatform or housing. The additional components of the drug deliverydevice, as described above, including the power and control system, theactivation mechanism, and the control arm may be attached, preformed, orpre-assembled to the assembly platform or housing. An adhesive patch andpatch liner may be attached to the housing surface of the drug deliverydevice that contacts the user during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a variable rate controlled delivery drive mechanismto drive fluid drug flow through the drug delivery device according to acontrolled rate or drug delivery profile. The method may further includethe step of: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the variable rate controlled delivery drivemechanism by the expansion of the biasing member acting upon a pistonwithin a drug container to force fluid drug flow through the drugcontainer, the fluid pathway connector, a sterile fluid conduit, and theinsertion mechanism for delivery of the fluid drug to the body of auser, wherein a drive gear or screw acting on the piston is utilized torestrain the free axial translation of the piston. The method ofoperation of the insertion mechanism and the drug delivery device may bebetter appreciated with reference to FIGS. 103A-103C, FIGS. 104A-104C,FIGS. 107A-107C, and FIGS. 108A-108C, as described above.

XV. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 80A-85C, 86A-91, 92-99, and 100A-109B may be configuredto incorporate the embodiments of the drive mechanism described below inconnection with FIGS. 69A-75B. The embodiments of the drive mechanismdescribed below in connection with FIGS. 69A-75B may be used to replace,in its entirety or partially, the above-described drive mechanism 100,6100, 8100, 9210, 9310, 9410, or 9510, or any other drive mechanismdescribed herein, where appropriate.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances, controlled drug delivery pumpswith such drive mechanisms, the methods of operating such devices, andthe methods of assembling such devices. Notably, the multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The novel embodiments of the present disclosurethus are capable of delivering drug substances at variable rates. Thedrive mechanisms of the present disclosure may be pre-configurable ordynamically configurable, such as by control by the power and controlsystem, to meet desired delivery rates or profiles, as explained indetail below. Additionally, the drive mechanisms of the presentdisclosure provide integrated status indication features which providefeedback to the user before, during, and after drug delivery. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. Because theend-of-dose indication is related to the physical end of axialtranslation and/or travel of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the novel devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a multi-functiondrive mechanism which includes an actuator, a gear assembly including amain gear, a drive housing, and a drug container having a cap, apierceable seal (not visible), a barrel, and a plunger seal. The maingear may be, for example, a star gear disposed to contact multiplesecondary gears or gear surfaces. A drug chamber, located within thebarrel between the pierceable seal and the plunger seal, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. A piston, and one or morebiasing members, wherein the one or more biasing members are initiallyretained in an energized state and is configured to bear upon aninterface surface of the piston, may also be incorporated in themulti-function drive mechanism. The piston is configured to translatesubstantially axially within a drug container having a plunger seal anda barrel. A tether is connected at one end to the piston and at anotherend to a winch drum/gear of a regulating mechanism, wherein the tetherrestrains the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The drug container may contain a drugfluid within a drug chamber for delivery to a user. Optionally, a coversleeve may be utilized between the biasing member and the interfacesurface of the piston to hide the interior components of the barrel(namely, the piston and the biasing member) from view during operationof the drive mechanism. The tether is configured to be released from awinch drum/gear of a regulating mechanism of the multi-function drivemechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In at least one embodiment of the present disclosure, the regulatingmechanism is gear assembly driven by an actuator of the multi-functiondrive mechanism. The regulating mechanism retards or restrains thedistribution of tether, only allowing it to advance at a regulated ordesired rate. This restricts movement of piston within barrel, which ispushed by one or more biasing members, hence controlling the movement ofplunger seal and delivery of the drug contained in chamber. As theplunger seal advances in the drug container, the drug substance isdispensed through the sterile pathway connection, conduit, insertionmechanism, and into the body of the user for drug delivery. The actuatormay be a number of power/motion sources including, for example, a motor(e.g., a DC motor, AC motor, or stepper motor) or a solenoid (e.g.,linear solenoid, rotary solenoid). In a particular embodiment, theactuator is a rotational stepper motor with a notch that correspondswith the gear teeth of the main/star gear.

The regulating mechanism may further include one or more gears of a gearassembly. One or more of the gears may be, for example, compound gearshaving a small diameter gear attached at a shared center point to alarge diameter gear. The gear assembly may include a winch gear coupledto a winch drum/gear upon which the tether may be releasably wound.Accordingly, rotation of the gear assembly initiated by the actuator maybe coupled to winch drum/gear (i.e., through the gear assembly), therebycontrolling the distribution of tether, the rate of expansion of thebiasing members and the axial translation of the piston, and the rate ofmovement of plunger seal within barrel to force a fluid from drugchamber. The rotational movement of the winch drum/gear, and thus theaxial translation of the piston and plunger seal, are metered,restrained, or otherwise prevented from free axial translation by othercomponents of the regulating element, as described herein. Notably, theregulating mechanisms of the present disclosure do not drive thedelivery of fluid substances from the drug chamber. The delivery offluid substances from the drug chamber is caused by the expansion of thebiasing member from its initial energized state acting upon the pistonand plunger seal. The regulating mechanisms instead function to provideresistance to the free motion of the piston and plunger seal as they arepushed by the expansion of the biasing member from its initial energizedstate. The regulating mechanism does not drive the delivery but onlycontrols the delivery motion. The tether limits or otherwise restrainsthe motion of the piston and plunger seal, but does not apply the forcefor the delivery.

In addition to controlling the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer (thereby delivering drug substances at variable rates and/ordelivery profiles); the multi-function drive mechanisms of the presentdisclosure may concurrently or sequentially perform the steps of:triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a user; and connecting a sterile fluid pathway to adrug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. In at least oneembodiment, initial motion by the actuator of the multi-function drivemechanism causes rotation of main/star gear. In one manner, main/stargear conveys motion to the regulating mechanism through gear assembly.In another manner, main/star gear conveys motion to the needle insertionmechanism through gear. As gear is rotated by main/star gear, gearengages the needle insertion mechanism to initiate the fluid pathwayconnector into the user, as described in detail above. In one particularembodiment, needle insertion mechanism is a rotational needle insertionmechanism. Accordingly, gear is configured to engage a correspondinggear surface of the needle insertion mechanism. Rotation of gear causesrotation of needle insertion mechanism through the gear interactionbetween gear of the drive mechanism and corresponding gear surface ofthe needle insertion mechanism. Once suitable rotation of the needleinsertion mechanism occurs, the needle insertion mechanism may beinitiated to create the fluid pathway connector into the user, asdescribed in detail herein.

In at least one embodiment, rotation of the needle insertion mechanismin this manner may also cause a connection of a sterile fluid pathway toa drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. Ramp aspect ofneedle insertion mechanism is caused to bear upon a movable connectionhub of the sterile fluid pathway connector. As the needle insertionmechanism is rotated by the multi-function drive mechanism, ramp aspectof needle insertion mechanism bears upon and translates movableconnection hub of the sterile fluid pathway connector to facilitate afluid connection therein. In at least one embodiment, the needleinsertion mechanism may be configured such that a particular degree ofrotation enables the needle/trocar to retract as detailed above.Additionally or alternatively, such needle/trocar retraction may beconfigured to occur upon a user-activity or upon movement or function ofanother component of the drug delivery device. In at least oneembodiment, needle/trocar retraction may be configured to occur uponend-of-drug-delivery, as triggered by, for example, the regulatingmechanism and/or one or more of the status readers as described herein.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug delivery pump having ahousing and an assembly platform, upon which an activation mechanism, aninsertion mechanism, a fluid pathway connector, a power and controlsystem, and a controlled delivery drive mechanism may be mounted, saiddrive mechanism having a drive housing, a piston, and a biasing member,wherein the biasing member is initially retained in an energized stateand is configured to bear upon an interface surface of the piston. Thepiston is configured to translate substantially axially within a drugcontainer having a plunger seal and a barrel. A tether is connected atone end to the piston and at another end to a winch drum/gear of adelivery regulating mechanism, wherein the tether restrains the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The drug container may contain a drug fluid within a drug chamberfor delivery to a user. Optionally, a cover sleeve may be utilizedbetween the biasing member and the interface surface of the piston tohide the interior components of the barrel (namely, the piston and thebiasing member) from view during operation of the drive mechanism. Thetether is configured to be released from a winch drum/gear of thedelivery regulating mechanism to meter the free expansion of the biasingmember from its initial energized state and the free axial translationof the piston upon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum/gear upon which the tether may be releasably wound, rotationof the winch drum/gear releases the tether from the winch drum/gear tometer the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The metering of the tether controls therate or profile of drug delivery to a user. The piston may be one ormore parts and connects to a distal end of the tether. The winchdrum/gear is coupled to a regulating mechanism which controls rotationof the winch drum/gear and hence metering of the translation of thepiston.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch drum/gear and thereby permit axialtranslation of the piston by the biasing member to translate a plungerseal within a barrel. The one or more inputs may be provided by theactuation of the activation mechanism, a control interface, and/or aremote control mechanism. The power and control system may be configuredto receive one or more inputs to adjust the restraint provided by thetether and winch drum/gear on the free axial translation of the pistonupon which the biasing member bears upon to meet a desired drug deliveryrate or profile, to change the dose volume for delivery to the user,and/or to otherwise start, stop, or pause operation of the drivemechanism.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of the actuator. The change in the rate of movement ofthe actuator causes a change in the rotation rate of the regulatingmechanism which, in turn, controls the rate of drug delivery to theuser. Alternatively, the delivery profile may be altered by a change inthe characteristics of the flow path of medicament through the conduitconnecting the drug container and insertion mechanism. The change may becaused by the introduction, removal, or modification of a flowrestrictor which restricts flow of medicament from the drug container tothe insertion mechanism. For example, a flow restrictor may havemultiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

The novel embodiments of the present disclosure provide drive mechanismswhich are capable of metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thereby, controlling therate of delivery of drug substances. The novel control delivery drivemechanisms are additionally capable of providing the incremental statusof the drug delivery before, during, and after operation of the device.Throughout this specification, unless otherwise indicated, “comprise,”“comprises,” and “comprising,” or related terms such as “includes” or“consists of,” are used inclusively rather than exclusively, so that astated integer or group of integers may include one or more othernon-stated integers or groups of integers. As will be described furtherbelow, the embodiments of the present disclosure may include one or moreadditional components which may be considered standard components in theindustry of medical devices. For example, the embodiments may includeone or more batteries utilized to power the motor, drive mechanisms, anddrug delivery devices of the present disclosure. The components, and theembodiments containing such components, are within the contemplation ofthe present disclosure and are to be understood as falling within thebreadth and scope of the present disclosure.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances and drug delivery pumps whichincorporate such multi-function drive mechanisms. The multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The drive mechanisms of the present disclosurecontrol the rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container and, thus, are capableof delivering drug substances at variable rates and/or deliveryprofiles. Additionally, the drive mechanisms of the present disclosureprovide integrated status indication features which provide feedback tothe user before, during, and after drug delivery. For example, the usermay be provided an initial feedback to identify that the system isoperational and ready for drug delivery. Upon activation, the system maythen provide one or more drug delivery status indications to the user.At completion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication.

The novel devices of the present disclosure provide drive mechanismswith integrated status indication and drug delivery pumps whichincorporate such drive mechanisms. Such devices are safe and easy touse, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. The novel devices of the presentdisclosure provide these desirable features without any of the problemsassociated with known prior art devices. Certain non-limitingembodiments of the novel drug delivery pumps, drive mechanisms, andtheir respective components are described further herein with referenceto the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.69A-69C show an exemplary drug delivery device according to at least oneembodiment of the present disclosure with the top housing removed sothat the internal components are visible. The drug delivery device maybe utilized to administer delivery of a drug treatment into a body of auser. As shown in FIGS. 69A-69C, the drug delivery device 9010 includesa pump housing 9012. Pump housing 9012 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug delivery device. Forexample, drug delivery device 9010 includes a pump housing 9012 whichmay include an upper housing and a lower housing (not shown for ease ofviewing internal components). The pump housing 9012 may include one ormore tamper evidence features to identify if the drug delivery devicehas been opened or tampered with. For example, the pump housing 9012 mayinclude one or more tamper evidence labels or stickers, such as labelsthat bridge across the upper housing and the lower housing. Additionallyor alternatively, the housing 9012 may include one or more snap arms orprongs connecting between the upper housing and the lower housing. Abroken or altered tamper evidence feature would signal to the user, thephysician, the supplier, the manufacturer, or the like, that the drugdelivery device has potentially been tampered, e.g., by accessing theinternal aspects of the device, so that the device is evaluated andpossibly discarded without use by or risk to the user. The drug deliverydevice may further include an activation mechanism, a status indicator,and a window. Window may be any translucent or transmissive surfacethrough which the operation of the drug delivery device may be viewed.As shown in FIG. 69B, drug delivery device 9010 further includesassembly platform 9020, sterile fluid conduit 9030, drive mechanism90100 having drug container 9050, insertion mechanism 90200, fluidpathway connector 90300, and a power and control system (not shown). Oneor more of the components of such drug delivery devices may be modularin that they may be, for example, pre-assembled as separate componentsand configured into position onto the assembly platform 9020 of the drugdelivery device 9010 during manufacturing.

The pump housing 9012 contains all of the device components and providesa means of removably attaching the device 9010 to the skin of the user.The pump housing 9012 also provides protection to the interiorcomponents of the device 9010 against environmental influences. The pumphousing 9012 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9012 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9012 may include certaincomponents, such as one or more status indicators and windows, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9010 provides anactivation mechanism that is displaced by the user to trigger the startcommand to the power and control system. In a preferred embodiment, theactivation mechanism is a start button that is located through the pumphousing 9012, such as through an aperture between upper housing andlower housing, and which contacts either directly or indirectly thepower and control system. In at least one embodiment, the start buttonmay be a push button, and in other embodiments, may be an on/off switch,a toggle, or any similar activation feature known in the art. The pumphousing 9012 also provides one or more status indicators and windows. Inother embodiments, one or more of the activation mechanism, the statusindicator, the window, and combinations thereof may be provided on theupper housing or the lower housing such as, for example, on a sidevisible to the user when the drug delivery device 9010 is placed on thebody of the user. Housing 9012 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device 9010 is configured such that, upon activation by auser by depression of the activation mechanism, the multi-function drivemechanism is activated to: insert a fluid pathway into the user; enable,connect, or open necessary connections between a drug container, a fluidpathway, and a sterile fluid conduit; and force drug fluid stored in thedrug container through the fluid pathway and fluid conduit for deliveryinto a user. In at least one embodiment, such delivery of drug fluidinto a user is performed by the multi-function drive mechanism in acontrolled manner. One or more optional safety mechanisms may beutilized, for example, to prevent premature activation of the drugdelivery device. For example, an optional on-body sensor (not visible)may be provided in one embodiment as a safety feature to ensure that thepower and control system, or the activation mechanism, cannot be engagedunless the drug delivery device 9010 is in contact with the body of theuser. In one such embodiment, the on-body sensor is located on thebottom of lower housing where it may come in contact with the user'sbody. Upon displacement of the on-body sensor, depression of theactivation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor is a mechanical safety mechanism, such asfor example a mechanical lock out, that prevents triggering of the drugdelivery device 9010 by the activation mechanism. In another embodiment,the on-body sensor may be an electro-mechanical sensor such as amechanical lock out that sends a signal to the power and control systemto permit activation. In still other embodiments, the on-body sensor canbe electrically based such as, for example, a capacitive- orimpedance-based sensor which must detect tissue before permittingactivation of the power and control system. These concepts are notmutually exclusive and one or more combinations may be utilized withinthe breadth of the present disclosure to prevent, for example, prematureactivation of the drug delivery device. In a preferred embodiment, thedrug delivery device 9010 utilizes one or more mechanical on-bodysensors. Additional integrated safety mechanisms are described hereinwith reference to other components of the novel drug delivery devices.

XV.A. Power and Control System:

The power and control system may include a power source, which providesthe energy for various electrical components within the drug deliverydevice, one or more feedback mechanisms, a microcontroller, a circuitboard, one or more conductive pads, and one or more interconnects. Othercomponents commonly used in such electrical systems may also beincluded, as would be appreciated by one having ordinary skill in theart. The one or more feedback mechanisms may include, for example,audible alarms such as piezo alarms and/or light indicators such aslight emitting diodes (LEDs). The microcontroller may be, for example, amicroprocessor. The power and control system controls several deviceinteractions with the user and interfaces with the drive mechanism90100. In one embodiment, the power and control system interfaces eitherdirectly or indirectly with the on-body sensor 9024 to identify when thedevice is in contact with the user and/or the activation mechanism toidentify when the device has been activated. The power and controlsystem may also interface with the status indicator of the pump housing9012, which may be a transmissive or translucent material which permitslight transfer, to provide visual feedback to the user. The power andcontrol system interfaces with the drive mechanism 90100 through one ormore interconnects to relay status indication, such as activation, drugdelivery, and end-of-dose, to the user. Such status indication may bepresented to the user via auditory tones, such as through the audiblealarms, and/or via visual indicators, such as through the LEDs. In apreferred embodiment, the control interfaces between the power andcontrol system and the other components of the drug delivery device arenot engaged or connected until activation by the user. This is adesirable safety feature that prevents accidental operation of the drugdelivery device and may additionally maintain the energy contained inthe power source during storage, transportation, and the like.

The power and control system may be configured to provide a number ofdifferent status indicators to the user. For example, the power andcontrol system may be configured such that after the on-body sensorand/or trigger mechanism have been pressed, the power and control systemprovides a ready-to-start status signal via the status indicator ifdevice start-up checks provide no errors. After providing theready-to-start status signal and, in an embodiment with the optionalon-body sensor, if the on-body sensor remains in contact with the bodyof the user, the power and control system will power the drive mechanism90100 to begin delivery of the drug treatment through the fluid pathwayconnector 90300 and sterile fluid conduit 9030 (not shown).

Additionally, the power and control system may be configured to identifyremoval of the drug delivery device from its packaging. The power andcontrol system may be mechanically, electronically, orelectro-mechanically connected to the packaging such that removal of thedrug delivery device from the packaging may activate or power-on thepower and control system for use, or simply enable the power and controlsystem to be powered-on by the user. In such an embodiment, withoutremoval of the drug delivery device from the packaging the drug deliverydevice cannot be activated. This provides an additional safety mechanismof the drug delivery device and for the user. In at least oneembodiment, the drug delivery device or the power and control system maybe electronically or electro-mechanically connected to the packaging,for example, such as by one or more interacting sensors from a range of:Hall effect sensors; giant magneto resistance (GMR) or magnetic fieldsensors; optical sensors; capacitive or capacitance change sensors;ultrasonic sensors; and linear travel, LVDT, linear resistive, orradiometric linear resistive sensors; and combinations thereof, whichare capable of coordinating to transmit a signal between components toidentify the location there-between. Additionally or alternatively, thedrug delivery device or the power and control system may be mechanicallyconnected to the packaging, such as by a pin and slot relationship whichactivates the system when the pin is removed (i.e., once the drugdelivery device is removed from the packaging).

In a preferred embodiment of the present disclosure, once the power andcontrol system has been activated, the multi-function drive mechanism isinitiated to actuate the insertion mechanism 90200 and the fluid pathwayconnector 90300, while also permitting the drug fluid to be forced fromthe drug container. During the drug delivery process, the power andcontrol system is configured to provide a dispensing status signal viathe status indicator. After the drug has been administered into the bodyof the user and after the end of any additional dwell time, to ensurethat substantially the entire dose has been delivered to the user, thepower and control system may provide an okay-to-remove status signal viathe status indicator. This may be independently verified by the user byviewing the drive mechanism and drug dose delivery through the window ofthe pump housing 9012. Additionally, the power and control system may beconfigured to provide one or more alert signals via the statusindicator, such as for example alerts indicative of fault or operationfailure situations.

The power and control system may additionally be configured to acceptvarious inputs from the user to dynamically control the drive mechanisms90100 to meet a desired drug delivery rate or profile. For example, thepower and control system may receive inputs, such as from partial orfull activation, depression, and/or release of the activation mechanism,to set, initiate, stop, or otherwise adjust the control of the drivemechanism 90100 via the power and control system to meet the desireddrug delivery rate or profile. Similarly, the power and control systemmay be configured to receive such inputs to adjust the drug dose volume;to prime the drive mechanism, fluid pathway connector, and fluidconduit; and/or to start, stop, or pause operation of the drivemechanism 90100. Such inputs may be received by the user directly actingon the drug delivery device 9010, such as by use of the activationmechanism 9014 or a different control interface, or the power andcontrol system may be configured to receive such inputs from a remotecontrol device. Additionally or alternatively, such inputs may bepre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism of the drugdelivery device 9010 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

XV.B. Insertion Mechanism

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure, including a rigid needle insertion mechanismand/or a rotational needle insertion mechanism as developed by theassignee of the present disclosure.

In at least one embodiment, the insertion mechanism 90200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 69B and FIG. 69C). The connection of the base to theassembly platform 9020 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9010. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9030 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9027 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane (not visible).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. Displacement of the lockoutpin(s), by one or more methods such as pulling, pushing, sliding, and/orrotation, permits insertion biasing member to decompress from itsinitial compressed, energized state. This decompression of the insertionbiasing member drives the needle and, optionally, the cannula into thebody of the user. At the end of the insertion stage or at the end ofdrug delivery (as triggered by the multi-function drive mechanism), theretraction biasing member is permitted to expand in the proximaldirection from its initial energized state. This axial expansion in theproximal direction of the retraction biasing member retracts the needle.If an inserter needle/trocar and cannula configuration are utilized,retraction of the needle may occur while maintaining the cannula influid communication with the body of the user. Accordingly, theinsertion mechanism may be used to insert a needle and cannula into theuser and, subsequently, retract the needle while retaining the cannulain position for drug delivery to the body of the user.

In at least one embodiment, as shown in FIG. 75A, the insertionmechanism includes a rotationally biased member 90210 which is initiallyheld in an energized state. In a preferred embodiment, the rotationallybiased member is a torsional spring. The rotational biasing member maybe prevented from de-energizing by interaction of gear surface 90208with gear 90112 or, alternatively, by contact of a component of theinsertion mechanism with a rotation prevention feature of the drugdelivery device. Upon activation of the device, or another input, therotationally biased member 90210 is permitted to, at least partially,de-energize. This causes one or more components of the insertionmechanism to rotate and, in turn, cause, or allow, the insertion of theneedle into the patient. Further, a cannula may be inserted into thepatient as described above. At a later time, such as when the controlarm or another component of the device recognizes a slack in the tether,the rotationally biased member may be allowed to further de-energize,causing additional rotation of one or more components of the insertionmechanism. This rotation may cause, or allow, the needle to be retractedfrom the patient. The needle may be fully retracted in a single step orthere may be multiple steps of retraction.

XV.C. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9010, the fluid pathway connector 90300 isenabled to connect the sterile fluid conduit 9030 to the drug containerof the drive mechanism 90100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 90100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user. In one such embodiment, the fluid pathway connector may besubstantially similar to that described in International PatentApplication No. PCT/US2012/054861, which is included by reference hereinin its entirety for all purposes. In such an embodiment, a compressiblesterile sleeve may be fixedly attached between the cap of the drugcontainer and the connection hub of the fluid pathway connector. Thepiercing member may reside within the sterile sleeve until a connectionbetween the fluid connection pathway and the drug container is desired.The sterile sleeve may be sterilized to ensure the sterility of thepiercing member and the fluid pathway prior to activation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Applications No.PCT/US2013/030478 or No. PCT/US2014/052329, for example, which areincluded by reference herein in their entirety for all purposes.According to such an embodiment, a drug container may have a drugchamber within a barrel between a pierceable seal and a plunger seal. Adrug fluid is contained in the drug chamber. Upon activation of thedevice by the user, a drive mechanism asserts a force on a plunger sealcontained in the drug container. As the plunger seal asserts a force onthe drug fluid and any air/gas gap or bubble, a combination of pneumaticand hydraulic pressure builds by compression of the air/gas and drugfluid and the force is relayed to the sliding pierceable seal. Thepierceable seal is caused to slide towards the cap, causing it to bepierced by the piercing member retained within the integrated sterilefluid pathway connector. Accordingly, the integrated sterile fluidpathway connector is connected (i.e., the fluid pathway is opened) bythe combination pneumatic/hydraulic force of the air/gas and drug fluidwithin the drug chamber created by activation of a drive mechanism. Oncethe integrated sterile fluid pathway connector is connected or opened,drug fluid is permitted to flow from the drug container, through theintegrated sterile fluid pathway connector, sterile fluid conduit, andinsertion mechanism, and into the body of the user for drug delivery. Inat least one embodiment, the fluid flows through only a manifold and acannula and/or needle of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery.

In a preferred embodiment, the sterile fluid pathway connector isinitiated by movement of the needle insertion mechanism, which itself isinitiated by the multi-function drive mechanism. Additionally oralternatively, the sterile fluid pathway connector is initiated bymovement directly of the multi-function drive mechanism. For example,the multi-function drive mechanism may include a rotational gear, suchas the star gear described in detail herein, that acts concurrently orsequentially to control the rate of drug delivery, to actuate the needleinsertion mechanism, and/or initiate the sterile fluid pathwayconnector. In one particular embodiment, shown in FIGS. 69A-69C, themulti-function drive mechanism performs all of these steps substantiallyconcurrently. The multi-function drive mechanism rotates a gear thatacts upon several other components. The gear acts on a gear assembly tocontrol the rate of drug delivery, while also contacting a needleinsertion mechanism to introduce a fluid pathway into the user. As theneedle insertion mechanism is initiated, the sterile fluid connection ismade to permit drug fluid flow from the drug container, through thefluid conduit, into the needle insertion mechanism, for delivery intothe patient as the gear and gear assembly of the multi-function drivemechanism control the rate of drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 90300 and the sterile fluid conduit 9030 are providedhereinafter in later sections in reference to other embodiments.

XV.D. Multi-Function Drive Mechanism:

The multi-function drive mechanisms of the present disclosure enable orinitiate several functions, including: (i) controlling the rate of drugdelivery by metering, providing resistance, or otherwise preventing freeaxial translation of the plunger seal utilized to force a drug substanceout of a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. With reference to the embodiments shown in FIGS.70A-70D and 71A-71D, multi-function drive mechanism 90100 includes anactuator 90101, a gear assembly 90110 including a main gear 90102, adrive housing 90130, and a drug container 9050 having a cap 9052, apierceable seal (not visible), a barrel 9058, and a plunger seal 9060.The main gear 90102 may be, for example, a star gear disposed to contactmultiple secondary gears or gear surfaces. A drug chamber 9021, locatedwithin the barrel 9058 between the pierceable seal and the plunger seal9060, may contain a drug fluid for delivery through the insertionmechanism and drug delivery device into the body of the user. The sealsdescribed herein may be comprised of a number of materials but are, in apreferred embodiment, comprised of one or more elastomers or rubbers.The drive mechanism 90100 may further contain one or more drive biasingmembers, one or more release mechanisms, and one or more guides, as aredescribed further herein. The components of the drive mechanism functionto force a fluid from the drug container out through the pierceableseal, or preferably through the piercing member of the fluid pathwayconnector, for delivery through the fluid pathway connector, sterilefluid conduit, and insertion mechanism into the body of the user.

In one particular embodiment, the drive mechanism 90100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. The fluid pathway connector may beconnected through the pierceable seal prior to, concurrently with, orafter activation of the drive mechanism to permit fluid flow from thedrug container, through the fluid pathway connector, sterile fluidconduit, and insertion mechanism, and into the body of the user for drugdelivery. In at least one embodiment, the fluid flows through only amanifold and a cannula of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detail herein.

Referring now to the embodiment of the multi-function drive mechanismshown in FIGS. 70A-70D and 71A-71D, multi-function drive mechanism 90100includes an actuator 90101, a gear assembly 90110 including a main gear90102, a drive housing 90130, and a drug container 9050 having a cap9052, a pierceable seal (not visible), a barrel 9058, and a plunger seal9060. The main gear 90102 may be, for example, a star gear disposed tocontact multiple secondary gears or gear surfaces. A drug chamber 9021,located within the barrel 9058 between the pierceable seal and theplunger seal 9060, may contain a drug fluid for delivery through theinsertion mechanism and drug delivery device into the body of the user.Compressed within the drive housing 90130, between the drug container9050 and the proximal end of the housing 90130, are one or more drivebiasing members 90122 and a piston 90110, wherein the drive biasingmembers 90122 are configured to bear upon an interface surface 90110C ofthe piston 90110, as described further herein. Optionally, a coversleeve (not shown) may be utilized between the drive biasing members90122 and the interface surface 90110C of the piston 90110 to, forexample, promote more even distribution of force from the drive biasingmember 90122 to the piston 90110, prevent buckling of the drive biasingmembers 90122, and/or hide biasing members 90122 from user view.Interface surface 90110C of piston 90110 is caused to rest substantiallyadjacent to, or in contact with, a proximal end of seal 9060. Althoughthe embodiments shown in FIGS. 70A-70D and 71A-71D show a singularbiasing member it is also contemplated that one or more biasing membersdisposed to act in parallel may be used.

As best shown in FIG. 70D and FIG. 71D, the piston 90110 may becomprised of two components 90110A and 90110B and have an interfacesurface 90110C to contact the plunger seal. A tether, ribbon, string, orother retention strap (referred to herein as the “tether” 90525) may beconnected at one end to the piston 90110A, 90110B. For example, thetether 90525 may be connected to the piston 90110A, 90110B by retentionbetween the two components of the piston 90110A, 90110B when assembled.The tether 90525 is connected at another end to a winch drum/gear 90520of a delivery control mechanism 90500. Through the use of the winchdrum/gear 90520 connected to one end of the tether 90525, and the tether90525 connected at another end to the piston 90110A, 90110B, theregulating mechanism 90500 functions to control, meter, provideresistance, or otherwise prevent free axial translation of the piston90110A, 90110B and plunger seal 9060 utilized to force a drug substanceout of a drug container 9050. Accordingly, the regulating mechanism90500 is a portion of the gear assembly 90116 aspect of themulti-function drive mechanism, which together function to control therate or profile of drug delivery to the user.

As shown in FIGS. 70A-70D and 71A-71D, and in isolation in FIGS. 72 and73A-73B, in the embodiments of the present disclosure, the regulatingmechanism 90500 is gear assembly driven by an actuator 90101 of themulti-function drive mechanism 90100. The regulating mechanism retardsor restrains the distribution of tether 90525, only allowing it toadvance at a regulated or desired rate. This restricts movement ofpiston 90110 within barrel 9058, which is pushed by one or more biasingmembers 90122, hence controlling the movement of plunger seal 9060 anddelivery of the drug contained in chamber 9021. As the plunger seal 9060advances in the drug container 9050, the drug substance is dispensedthrough the sterile pathway connection 90300, conduit 9030, insertionmechanism 90200, and into the body of the user for drug delivery. Theactuator 90101 may be a number of power/motion sources including, forexample, a solenoid, a stepper motor, or a rotational drive motor. In aparticular embodiment, the actuator 90101 is a rotational stepper motorwith a notch that corresponds with the gear teeth of the main/star gear90102. Commonly, such a rotational stepper motor may be referred to as a‘Pac-Man’ motor. In at least one embodiment, the Pac-Man motor has agear interface within which one or more teeth of the main gear maypartially reside during operation of the system. This is more clearlyvisible in FIGS. 73A-73B. When the gear interface 90101A of the Pac-Manmotor 90101 is in alignment with a tooth 90102A of the main gear 90102,rotational motion of the Pac-Man motor 90101 causes gear interfacerotation of the main gear 90102. When the Pac-Man motor 90101 is betweengear teeth of the main gear, it may act as a resistance for, forexample, back-spinning or unwinding of the gear assembly 90116. In oneparticular embodiment, the Pac-Man motor 90101 utilizes an alternatingdirection type motor to rotate the Pac-Man motor 90101 backwards andforwards. This configuration aids in the prevention of a runawaycondition, where the motor and the gears are freely permitted to rotate,by using the multi-direction of the motor to prevent continuous spin inone direction (as would be needed for a runaway condition). Thisbi-directional movement of the motor, coupled with the use of the gearinterface cut within the Pac-Man motor, provide suitable safety featuresto prevent a runaway condition that could potentially lead toover-delivery of drug to the user. Further detail about the gearassembly 90116, regulating mechanism 90500, and multi-function drivemechanism 90100 are provided herein.

In a particular embodiment shown in FIGS. 73A-73B, the regulatingelement 90500 further includes one or more gears 90511, 90512, 90513,90514, of a gear assembly 90516. One or more of the gears 90511, 90512,90513, 90514 may be, for example, compound gears having a small diametergear attached at a shared center point to a large diameter gear. Gear90513 may be rotationally coupled to winch drum/gear 90520, for exampleby a keyed shaft, thereby coupling rotation of gear assembly 90516 towinch drum/gear 90520. Compound gear 90512 engages the small diametergear 90513 such that rotational movement of the compound gear aspect90512B is conveyed by engagement of the gears (such as by engagement ofcorresponding gear teeth) to gear 90513. Compound gear aspect 90512A,the rotation of which is coupled to gear aspect 90512B, is caused torotate by action of compound gear aspect 90102B of the main/star gear90102. Compound gear aspect 90102B, the rotation of which is coupled tomain/star gear 90102, is caused to rotate by interaction betweenmain/star gear 90102A and interface 90101A of the actuator 90101. Thus,rotation of main/star gear 90102 is conveyed to winch drum/gear 90520.Accordingly, rotation of the gear assembly 90516 initiated by theactuator 90101 may be coupled to winch drum/gear 90520 (i.e., throughthe gear assembly 90516), thereby controlling the distribution of tether90525, and the rate of movement of plunger seal 9060 within barrel 9058to force a fluid from drug chamber 9021. The rotational movement of thewinch drum/gear 90520, and thus the axial translation of the piston90110 and plunger seal 9060, are metered, restrained, or otherwiseprevented from free axial translation by other components of theregulating element 90500, as described herein. As described above, theactuator 90101 may be a number of known power/motion sources including,for example, a motor (e.g., a DC motor, AC motor, or stepper motor) or asolenoid (e.g., linear solenoid, rotary solenoid).

The embodiment described above and shown in FIGS. 69A-73D show anactuator 90101 that is in vertical alignment and in direct engagementwith the main/star gear 90102. As would readily be appreciated by onehaving ordinary skill in the mechanical arts, the actuator 90101 couldbe modified to be in horizontal alignment. Additionally oralternatively, the actuator 90101 could be modified to be in indirectengagement with the main/star gear 90102. The embodiments shown in FIGS.75A-75B show an actuator 90101 that is in horizontal alignment andindirect engagement with the main/star gear 90102. Such an embodimentmay utilize a rack and pinion engagement, a drive screw, or a worm gear90101W, as shown in FIGS. 75A-75B, to change the direction of motionfrom horizontal to vertical (i.e., perpendicular interaction). Actuator90101 rotates worm gear 90101W, which engages gear 90101G and conveysthe motion to the Pac-Man gear 90101A. The Pac-Man gear 90101A engagesmain/star gear 90102 to enable operation of the drive mechanism and thedrug delivery device, as described herein. Main/star gear 90102 alsodrives operation of gear 90112 to enable operation of the needleinsertion mechanism 90200, as described herein. In one particularembodiment, the actuator 90101 utilizes an alternating direction typemotor to rotate the worm gear 90101W, gear 90101G, and Pac-Man gear90101A backwards and forwards. This configuration aids in the preventionof a runaway condition, where the motor and the gears are freelypermitted to rotate, by using the multi-direction of the motor toprevent continuous spin in one direction (as would be needed for arunaway condition). This bi-directional movement of the actuator 90101,coupled with the use of the gear interface of the worm gear 90101W, gear90101G, and Pac-Man gear 90101A with the main/star gear 90102, providesuitable safety features to prevent a runaway condition that couldpotentially lead to over-delivery of drug to the user. Additionally, theactuator 90101 may include a stop member 90101B that stops the rotationof the Pac-Man gear 90101A against a stop block 90150. Stop block 90150further prevents over-rotation of the Pac-Man gear 90101A and,accordingly, the main/star gear 90102 to prevent a runaway conditionthat could potentially lead to over-delivery of drug to the user. Forthe device to function in this configuration, the Pac-Man gear 90101Amust be rotated backwards the other direction before rotating forwardsagain to progress the main/star gear 90102 because the stop member90101B prevents over rotation in one direction by interaction with thestop block 90150. Additionally, the geometry of worm gear 90101W may beconfigured such that it is self-locking and/or cannot be back-driven bygear 90101G. This may be done by configuration of parameters such as:pitch, lead angle, pressure angle, and number of threads. In so doing,runaway conditions of the drive mechanism will be prevented by the wormgear's resistance to rotations that are not caused by actuator 90101.

Notably, the regulating mechanisms 90500 of the present disclosure donot drive the delivery of fluid substances from the drug chamber 9021.The delivery of fluid substances from the drug chamber 9021 is caused bythe expansion of the biasing member 90122 from its initial energizedstate acting upon the piston 90110A, 90110B and plunger seal 9060. Theregulating mechanisms 90500 instead function to provide resistance tothe free motion of the piston 90110A, 90110B and plunger seal 9060 asthey are pushed by the expansion of the biasing member 90122 from itsinitial energized state. The regulating mechanism 90500 does not drivethe delivery but only controls the delivery motion. The tether limits orotherwise restrains the motion of the piston 90110 and plunger seal9060, but does not apply the force for the delivery. According to apreferred embodiment, the controlled delivery drive mechanisms and drugdelivery devices of the present disclosure include a regulatingmechanism indirectly or directly connected to a tether metering theaxial translation of the piston 90110A, 90110B and plunger seal 9060,which are being driven to axially translate by the biasing member 90122.The rate of drug delivery as controlled by the regulating mechanism maybe determined by: selection of the gear ratio of gear assembly 90516;selection of the main/star gear 90102; selection of the diameter ofwinding drum/gear 90520; using electromechanical actuator 90101 tocontrol the rate of rotation of the main/star gear 90102; or any othermethod known to one skilled in the art. By using electromechanicalactuator 90101 the rate of rotation of the main/star gear 90102 it maybe possible to configure a drug delivery device to provide a variabledose rate (i.e., the rate of drug delivery is varied during atreatment).

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether 90525 by the winch drum/gear 90520 and thereby permitaxial translation of the piston 90110 by the biasing member 90122 totranslate a plunger seal 9060 within a barrel 9058. The one or moreinputs may be provided by the actuation of the activation mechanism, acontrol interface, and/or a remote control mechanism. The power andcontrol system may be configured to receive one or more inputs to adjustthe restraint provided by the tether 90525 and winch drum/gear 90520 onthe free axial translation of the piston 90110 upon which the biasingmember 90122 bears upon to meet a desired drug delivery rate or profile,to change the dose volume for delivery to the user, and/or to otherwisestart, stop, or pause operation of the drive mechanism.

The components of the drive mechanism 90100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9060 of the drug container 9050. Optionally, the drive mechanism90100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9060 to, for example,ensure that substantially the entire drug dose has been delivered to theuser. For example, the plunger seal 9060, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user.

The tether 90525 may have one or more status triggers, such aselectrical contacts, optical markings, or electromechanical pins orrecesses, which are capable of contacting or being recognized by astatus reader. In at least one embodiment, an end-of-dose statusindication may be provided to the user once the status reader contactsor recognizes the final status trigger positioned on the tether 90525that would contact the status reader at the end of axial travel of thepiston 90110A, 90110B and plunger 9060 within the barrel 9058 of thedrug container 9050. The status reader may be, for example, anelectrical switch reader to contact the corresponding electricalcontacts, an optical reader to recognize the corresponding opticalmarkings, or a mechanical or electromechanical reader configured tocontact corresponding pins, holes, or similar aspects on the tether. Thestatus triggers may be positioned along the tether 90525 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asthe drug delivery device is activated and drug delivery is begun byrelease of the biasing member 90122 and the resulting force applied tothe piston 90110A, 90110B and plunger seal 9060, the rate or profile ofdrug delivery to the user is controlled by the regulating mechanism90500, gear assembly 90516, and winch drum/gear 90520 releasing thetether 90525 and permitting expansion of the biasing member 90122 andaxial translation of the piston 90110A, 90110B and plunger seal 9060. Asthis occurs, the status triggers of the tether 90525 are contacted orrecognized by the status reader and the status of the drive mechanismbefore, during, and after operation can be relayed to the power andcontrol system to provide feedback to the user. Depending on the numberof status triggers located on the tether 90525, the frequency of theincremental status indication may be varied as desired. As describedabove, a range of status readers may be utilized depending on the statustriggers utilized by the system.

In a preferred embodiment, the status reader may apply a tensioningforce to the tether 90525. When the system reaches end-of-dose, thetether 90525 goes slack and the status reader 90544 is permitted torotate about a fulcrum. This rotation may operate an electrical orelectromechanical switch, for example a switch, signaling slack in thetether 90525 to the power and control system. Additionally, a gear 90511of gear assembly 90516 may act as an encoder along with a sensor. Thesensor/encoder combination is used to provide feedback of gear assemblyrotation, which in turn can be calibrated to the position of piston90110 when there is no slack in the tether 90525. Together, the statusreader and sensor/encoder may provide positional feedback, end-of-dosesignal, and error indication, such as an occlusion, by observing slackin the tether 90525 prior to reaching the expected number of motorrotations as counted by the sensor/encoder.

Additional means may exist for terminating or restraining the flow ofthe medicament in the case of slack in, or failure of, the tether. FIGS.74A-74B show one such embodiment. Disposed within barrel 9058 are brake9064, sleeve 9062, and plug 9068, and optionally retainer 9066. Biasingmember 90122 bears against sleeve 9062. Tether 90525 is engaged withplug 9068, thereby allowing tether 90525 to restrain the motion ofsleeve 9062. This restraint controls the rate of expansion orde-energizing of biasing member 90122. When tether 90525 is undertension, plug 9068 bears against distal face 9064A of brake 9064,causing proximal face 9064B of brake 9064 to bear against sleeve 9062.Due to this contact, and the profile of the distal end 9062A of sleeve9062, brake 9064 is maintained in a substantially conical configurationas shown in FIG. 74A. In this configuration, expansion or de-energizingof biasing member 90122 is restrained. Also, in this conicalconfiguration, the outer diameter of brake 9064 is less than the innerdiameter of barrel 9058, thus translation of the brake is not restrainedby contact with the inner wall of the drug container. Also, a portion ofbrake 9064 is in contact with retainer 9066. Because brake 9064 ismaintained in this configuration by plug 9068 and sleeve 9062,translation of sleeve 9062, caused by decompression of biasing member90122, is transferred to retainer 9066. Likewise, contact of retainer9066 with plunger seal 9060 causes translation of plunger seal 9060.

As shown in FIG. 74B, in the event of slack in, or failure of, tether90525, plug 9068 is no longer held in position by tether 90525 and,therefore, no longer restrains motion of sleeve 9062. As biasing member90122 decompresses or de-energizes, brake 9064 transforms to arelatively less conical or flatter configuration. This may be caused bya natural bias of brake 9064 to transform to this configuration or,alternatively, may be caused by contact of brake 9064 with both retainer9066 and sleeve 9062. As the brake is transformed, it comes into contactwith the inner wall of barrel 9058. The brake thus acts as a wedge torestrict translation of sleeve 9062. This may prevent furthertranslation or may act to restrict the rate of translation. Optionally,restoring tension in the tether may cause the plug to contact the brakeand to transform the brake back to its conical configuration and thusrestore normal operation of the drug delivery device.

FIGS. 74A-74B show the plug as having a spherical shape and the brake ashaving a conical shape. Such shapes are used herein merely for exemplarypurposes and other shapes or configurations could readily be utilized toachieve the same or similar functionality. For example, the plug mayitself be conical in shape and, in one embodiment, be shaped tointerface the brake when the brake is in a conical shape. In such aconfiguration, the conical shape of the plug assists in maintaining theconical shape of the brake, thereby preventing contact between the outerdiameter of the brake with the inner diameter of the barrel in order torestrict the axial translation of the sleeve 9062 (i.e., applying abraking force). In another embodiment, the brake 9064 could employ astar-shaped or other configuration when in a substantially flattenedposition so as to make contact with the inner diameter of the barrel9058 to prevent or restrict further axial translation of sleeve 9062.Without further translation of sleeve 9062, biasing member 90122 cannotexpand or de-energize further which, in turn, prevents or restrictsfurther drug delivery to the user. This provides a necessary and usefulsafety measure for drug delivery, to prevent over-delivery oraccelerated delivery of drug to the user.

Referring back to FIGS. 70A-70D and 71A-71D, in addition to controllingthe rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container (thereby deliveringdrug substances at variable rates and/or delivery profiles); themulti-function drive mechanisms of the present disclosure mayconcurrently or sequentially perform the steps of: triggering a needleinsertion mechanism to provide a fluid pathway for drug delivery to auser; and connecting a sterile fluid pathway to a drug container topermit fluid flow from the drug container to the needle insertionmechanism for delivery to the user. In at least one embodiment, as shownin FIGS. 70A-70D and 71A-71D, initial motion by the actuator 90101 ofthe multi-function drive mechanism 90100 causes rotation of main/stargear 90102. Main/star gear 90102 is shown as a compound gear withaspects 90102A and 90102B (see FIG. 72). In one manner, main/star gear90102 conveys motion to the regulating mechanism 90500 through gearassembly 90516. In another manner, main/star gear 90102 conveys motionto the needle insertion mechanism 90200 through gear 90112. As gear90112 is rotated by main/star gear 90102, gear 90112 engages the needleinsertion mechanism 90200 to initiate the fluid pathway connector intothe user, as described in detail above. In one particular embodiment,needle insertion mechanism 90200 is a rotational needle insertionmechanism. Accordingly, gear 90112 is configured to engage acorresponding gear surface 90208 of the needle insertion mechanism90200. Rotation of gear 90112 causes rotation of needle insertionmechanism 90200 through the gear interaction between gear 90112 of thedrive mechanism 90100 and corresponding gear surface 90208 of the needleinsertion mechanism 90200. Once suitable rotation of the needleinsertion mechanism 90200 occurs, for example rotation along axis ‘R’shown in FIG. 2B-2C, the needle insertion mechanism may be initiated tocreate the fluid pathway connector into the user, as described in detailabove. In an alternative embodiment, as shown in FIGS. 75A-75B, gear90112 may indirectly engage the needle insertion mechanism 90200 toinitiate the fluid pathway connector into the user. For example, gear90112 may be configured to engage a corresponding gear surface of acontrol arm 90202 (visible in FIG. 75B) that contacts or blocks theneedle insertion mechanism 90200. Rotation of gear 90112 causes movementof the control arm 90202, which may initiate or permit rotation ofneedle insertion mechanism 90200. Such a needle insertion mechanism, asshown in FIGS. 75A-75B, includes a rotationally biased member 90210which is initially held in an energized state. The rotational biasingmember may be prevented from de-energizing by contact of a component ofthe insertion mechanism with a rotation prevention feature, such as ablocking aspect of the control arm, of the drug delivery device. Uponactivation of the device, or another input, the rotationally biasedmember 90210 is permitted to, at least partially, de-energize. Thiscauses one or more components of the insertion mechanism to rotate and,in turn, cause, or allow, the insertion of the needle into the patient.Further, a cannula may be inserted into the patient as described above.At a later time, such as when the control arm or another component ofthe device recognizes a slack in the tether 90525, the rotationallybiased member may be allowed to further de-energize, such as by furtherinteraction with the control arm, causing additional rotation of one ormore components of the insertion mechanism. This rotation may cause, orallow, the needle to be retracted from the patient. The needle may befully retracted in a single step or there may be multiple steps ofretraction.

As shown in FIGS. 70A-70D and 71A-71D, rotation of the needle insertionmechanism 90200 in this manner may also cause a connection of a sterilefluid pathway to a drug container to permit fluid flow from the drugcontainer to the needle insertion mechanism for delivery to the user.Ramp aspect 90222 of needle insertion mechanism 90200 is caused to bearupon a movable connection hub 90322 of the sterile fluid pathwayconnector 90300. As the needle insertion mechanism 90200 is rotated bythe multi-function drive mechanism 90100, ramp aspect 90222 of needleinsertion mechanism 90200 bears upon and translates movable connectionhub 90322 of the sterile fluid pathway connector 90300 to facilitate afluid connection therein. Such translation may occur, for example, inthe direction of the hollow arrow along axis ‘C’ shown in FIGS. 70B and71B. In at least one embodiment, the needle insertion mechanism 90200may be configured such that a particular degree of rotation uponrotational axis ‘R’ (shown in FIGS. 70B-70C) enables the needle/trocarto retract as detailed above. Additionally or alternatively, suchneedle/trocar retraction may be configured to occur upon a user-activityor upon movement or function of another component of the drug deliverydevice. In at least one embodiment, needle/trocar retraction may beconfigured to occur upon end-of-drug-delivery, as triggered by, forexample, the regulating mechanism 90500 and/or one or more of the statusreaders as described above. During these stages of operation, deliveryof fluid substances from the drug chamber 9021 may be initiated,on-going, and/or completed by the expansion of the biasing member 90122from its initial energized state acting upon the piston 90110A, 90110Band plunger seal 9060. As described above, the regulating mechanisms90500 function to provide resistance to the free motion of the piston90110A, 90110B and plunger seal 9060 as they are pushed by the expansionof the biasing member 90122 from its initial energized state. Theregulating mechanism 90500 does not drive the delivery but only controlsthe delivery motion. The tether limits or otherwise restrains the motionof the piston 90110 and plunger seal 9060, but does not apply the forcefor the delivery. This is visible through the progression of thecomponents shown in FIGS. 70A-70D and 71A-71D. The motion of the piston90110A, 90110B and plunger seal 9060 as they are pushed by the expansionof the biasing member 90122 from its initial energized state are shownin the direction of the solid arrow along axis ‘A’ from proximal orfirst position ‘P’ to the distal or second position ‘D’, as shown in thetransition of FIGS. 70A-70D and 71A-71D.

Further aspects of the novel drive mechanism will be described withreference to FIG. 72 and FIGS. 73A-73B. FIG. 72 shows a perspective viewof the multi-function drive mechanism, according to at least a firstembodiment, during its initial locked stage. Initially, the tether 90525may retain the biasing member 90122 in an initial energized positionwithin piston 90110A, 90110B. Directly or indirectly upon activation ofthe device by the user, the multi-function drive mechanism 90100 may beactivated to permit the biasing member to impart a force to piston 90110and therefore to tether 90525. This force on tether 90525 imparts atorque on winding drum 90520 which causes the gear assembly 90516 andregulating mechanism 90500 to begin motion. As shown in FIG. 73A, thepiston 90110 and biasing member 90122 are both initially in acompressed, energized state behind the plunger seal 9060. The biasingmember 90122 may be maintained in this state until activation of thedevice between internal features of drive housing 90130 and interfacesurface 90110C of piston 90110A, 90110B. As the drug delivery device9010 is activated and the drive mechanism 90100 is triggered to operate,biasing member 90122 is permitted to expand (i.e., decompress) axiallyin the distal direction (i.e., in the direction of the solid arrow shownin FIGS. 70A-70D and FIGS. 71A-71D). Such expansion causes the biasingmember 90122 to act upon and distally translate interface surface 90110Cand piston 90110, thereby distally translating plunger seal 9060 to pushdrug fluid out of the drug chamber 9021 of barrel 9058. In at least oneembodiment, an end-of-dose status indication may be provided to the useronce the status reader contacts or recognizes a status triggerpositioned on the tether 90525 to substantially correspond with the endof axial travel of the piston 90110A, 90110B and plunger seal 9060within the barrel 9058 of the drug container 9050. The status triggersmay be positioned along the tether 90525 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the user. In at least one embodiment,the status reader is an optical status reader configured to recognizethe corresponding optical status triggers on the tether. As would beunderstood by an ordinarily skilled artisan, such optical statustriggers may be markings which are recognizable by the optical statusreader. In another embodiment, the status reader is a mechanical orelectromechanical reader configured to physically contact correspondingpins, holes, or similar aspects on the tether. Electrical contacts couldsimilarly be utilized on the tether as status indicators which contactor are otherwise recognized by the corresponding electrical statusreader. The status triggers may be positioned along the tether 90525 tobe read or recognized at positions which correspond with the beginningand end of drug delivery, as well as at desired increments during drugdelivery. As shown, tether 90525 passes substantially axially throughthe drive mechanism housing 90130, the biasing member 90122, andconnects to the piston 90110 A, 90110B to restrict the axial translationof the piston 90110A, 90110B and the plunger seal 9060 that residesadjacent thereto.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement ofwinding drum 90520 and, thus, axial translation of the components of thecontrolled delivery drive mechanism 90100. Accordingly, the regulatingmechanism 90500 only controls the motion of the drive mechanism, butdoes not apply the force for the drug delivery. One or more additionalbiasing members 90122, such as compression springs, may be utilized todrive or assist the driving of the piston 90110. For example, acompression spring may be utilized within the drive housing 90130 forthis purpose. The regulating mechanism 90500 only controls, meters, orregulates such action. The controlled delivery drive mechanisms and/ordrug delivery devices of the present disclosure may additionally enablea compliance push to ensure that substantially all of the drug substancehas been pushed out of the drug chamber 9021. The plunger seal 9060,itself, may have some compressibility permitting a compliance push ofdrug fluid from the drug container. For example, when a pop-out plungerseal is employed, i.e., a plunger seal that is deformable from aninitial state, the plunger seal may be caused to deform or “pop-out” toprovide a compliance push of drug fluid from the drug container.Additionally or alternatively, an electromechanical status switch andinterconnect assembly may be utilized to contact, connect, or otherwiseenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

In at least one embodiment, incremental status indication may beprovided to the user by reading or recognizing the rotational movementof one or more gears of gear assembly 90516. As the gear assembly 90516rotates, a status reader may read or recognize one or more correspondingstatus triggers on one of the gears in the gear assembly to provideincremental status indication before, during, and after operation of thevariable rate controlled delivery drive mechanism. A number of statusreaders may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism may utilize a mechanicalstatus reader which is physically contacted by gear teeth of one of thegears of the gear assembly. As the status reader is contacted by thestatus trigger(s), which in this exemplary embodiment may be the gearteeth of one of the gears (or holes, pins, ridges, markings, electricalcontacts, or the like, upon the gear), the status reader measures therotational position of the gear and transmits a signal to the power andcontrol system for status indication to the user. Additionally oralternatively, the drive mechanism may utilize an optical status reader.The optical status reader may be, for example, a light beam that iscapable of recognizing a motion and transmitting a signal to the powerand control system. For example, the drive mechanism may utilize anoptical status reader that is configured to recognize motion of the gearteeth of one of the gears in the gear assembly (or holes, pins, ridges,markings, electrical contacts, or the like, upon the gear). Similarly,the status reader may be an electrical switch configured to recognizeelectrical contacts on the gear. In any of these embodiments, the sensormay be utilized to then relay a signal to the power and control systemto provide feedback to the user.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to the user.While the drive mechanisms of the present disclosure are described withreference to the gear assembly and regulating mechanism shown in thefigures, a range of configurations may be acceptable and capable ofbeing employed within the embodiments of the present disclosure, aswould readily be appreciated by an ordinarily skilled artisan.Accordingly, the embodiments of the present disclosure are not limitedto the specific gear assembly and regulating mechanism described herein,which is provided as an exemplary embodiment of such mechanisms foremployment within the controlled delivery drive mechanisms and drugdelivery pumps.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of actuator 90101. The change in the rate of movementof actuator 90101 causes a change in the rotation rate of regulatingmechanism 90500 which, in turn, controls the rate of drug delivery tothe user. Alternatively, the delivery profile may be altered by a changein the characteristics of the flow path of medicament through theconduit connecting the drug container and insertion mechanism. Thechange may be caused by the introduction, removal, or modification of aflow restrictor which restricts flow of medicament from the drugcontainer to the insertion mechanism. For example, a flow restrictor mayhave multiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

Assembly and/or manufacturing of controlled delivery drive mechanism90100, drug delivery device 9010, or any of the individual componentsmay utilize a number of known materials and methodologies in the art.For example, a number of known cleaning fluids such as isopropyl alcoholand hexane may be used to clean the components and/or the devices. Anumber of known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9050 may first be assembledand filled with a fluid for delivery to the user. The drug container9050 includes a cap 9052, a pierceable seal 9056, a barrel 9058, and aplunger seal 9060. The pierceable seal 9056 may be fixedly engagedbetween the cap 9052 and the barrel 9058, at a distal end of the barrel9058. The barrel 9058 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9060 from theproximal end of the barrel 9058. An optional connection mount 9054 maybe mounted to a distal end of the pierceable seal 9056. The connectionmount 9054 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9058 of the drug container 9050. Thedrug container 9050 may then be mounted to a distal end of drive housing90130.

One or more drive biasing members 90122 may be inserted into a distalend of the drive housing 90130. Optionally, a cover sleeve 90140 may beinserted into a distal end of the drive housing 90130 to substantiallycover biasing member 90122. A piston may be inserted into the distal endof the drive housing 90130 such that it resides at least partiallywithin an axial pass-through of the biasing member 90122 and the biasingmember 90122 is permitted to contact a piston interface surface 90110Cof piston 90110A, 90110B at the distal end of the biasing member 90122.An optional cover sleeve 90140 may be utilized to enclose the biasingmember 90122 and contact the piston interface surface 90110C of piston90110A, 90110B. The piston 90110A, 90110B and drive biasing member90122, and optional cover sleeve 90140, may be compressed into drivehousing 90130. Such assembly positions the drive biasing member 90122 inan initial compressed, energized state and preferably places a pistoninterface surface 90110C in contact with the proximal surface of theplunger seal 9060 within the proximal end of barrel 9058. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 90130 prior to attachment or mounting of the drug container9050. The tether 90525 is pre-connected to the proximal end of thepiston 90110A, 90110B and passed through the axial aperture of thebiasing member 90122 and drive mechanism 90130, and then wound throughthe interior of the drug delivery device with the other end of thetether 90525 wrapped around the winch drum/gear 90520 of the regulatingmechanism 90500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 69B.

Certain optional standard components or variations of drive mechanism90100 or drug delivery device 9010 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9018 to enablethe user to view the operation of the drug delivery device 9010 orverify that drug dose has completed. Similarly, the drug delivery device9010 may contain an adhesive patch 9026 and a patch liner 9028 on thebottom surface of the housing 9012. The adhesive patch 9026 may beutilized to adhere the drug delivery device 9010 to the body of the userfor delivery of the drug dose. As would be readily understood by onehaving ordinary skill in the art, the adhesive patch 9026 may have anadhesive surface for adhesion of the drug delivery device to the body ofthe user. The adhesive surface of the adhesive patch 9026 may initiallybe covered by a non-adhesive patch liner 9028, which is removed from theadhesive patch 9026 prior to placement of the drug delivery device 9010in contact with the body of the user. Removal of the patch liner 9028may further remove the sealing membrane 90254 of the insertion mechanism90200, opening the insertion mechanism to the body of the user for drugdelivery (as shown in FIG. 69C).

Similarly, one or more of the components of controlled delivery drivemechanism 90100 and drug delivery device 9010 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9010 is shown as two separate components upper housing9012A and lower housing 9012B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The novel controlleddelivery drive mechanisms of the present disclosure may be directly orindirectly activated by the user. Furthermore, the novel configurationsof the controlled delivery drive mechanism and drug delivery devices ofthe present disclosure maintain the sterility of the fluid pathwayduring storage, transportation, and through operation of the device.Because the path that the drug fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe drug container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent disclosure do not require terminal sterilization upon completionof assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connection, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a user, wherein aregulating mechanism acting to restrain the distribution of a tether isutilized to meter the free axial translation of the piston. The methodof operation of the drive mechanism and the drug delivery device may bebetter appreciated with reference to FIGS. 70A-70D and FIGS. 71A-71D, asdescribed above.

XVI. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 80A-85C, 86A-91, 92-99, and 100A-109B may be configuredto incorporate the embodiments of the drive mechanism described below inconnection with FIGS. 69A-75B. The embodiments of the drive mechanismdescribed below in connection with FIGS. 69A-75B may be used to replace,in its entirety or partially, the above-described drive mechanism 100,6100, 8100, 9210, 9310, 9410, or 9510, or any other drive mechanismdescribed herein, where appropriate.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances, controlled drug delivery pumpswith such drive mechanisms, the methods of operating such devices, andthe methods of assembling such devices. Notably, the multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The novel embodiments of the present disclosurethus are capable of delivering drug substances at variable rates. Thedrive mechanisms of the present disclosure may be pre-configurable ordynamically configurable, such as by control by the power and controlsystem, to meet desired delivery rates or profiles, as explained indetail below. Additionally, the drive mechanisms of the presentdisclosure provide integrated status indication features which providefeedback to the user before, during, and after drug delivery. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. Because theend-of-dose indication is related to the physical end of axialtranslation and/or travel of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the novel devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a multi-functiondrive mechanism which includes an actuator, a gear assembly including amain gear, a drive housing, and a drug container having a cap, apierceable seal (not visible), a barrel, and a plunger seal. The maingear may be, for example, a star gear disposed to contact multiplesecondary gears or gear surfaces. A drug chamber, located within thebarrel between the pierceable seal and the plunger seal, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. A piston, and one or morebiasing members, wherein the one or more biasing members are initiallyretained in an energized state and is configured to bear upon aninterface surface of the piston, may also be incorporated in themulti-function drive mechanism. The piston is configured to translatesubstantially axially within a drug container having a plunger seal anda barrel. A tether is connected at one end to the piston and at anotherend to a winch drum/gear of a regulating mechanism, wherein the tetherrestrains the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The drug container may contain a drugfluid within a drug chamber for delivery to a user. Optionally, a coversleeve may be utilized between the biasing member and the interfacesurface of the piston to hide the interior components of the barrel(namely, the piston and the biasing member) from view during operationof the drive mechanism. The tether is configured to be released from awinch drum/gear of a regulating mechanism of the multi-function drivemechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In at least one embodiment of the present disclosure, the regulatingmechanism is gear assembly driven by an actuator of the multi-functiondrive mechanism. The regulating mechanism retards or restrains thedistribution of tether, only allowing it to advance at a regulated ordesired rate. This restricts movement of piston within barrel, which ispushed by one or more biasing members, hence controlling the movement ofplunger seal and delivery of the drug contained in chamber. As theplunger seal advances in the drug container, the drug substance isdispensed through the sterile pathway connection, conduit, insertionmechanism, and into the body of the user for drug delivery. The actuatormay be a number of power/motion sources including, for example, a motor(e.g., a DC motor, AC motor, or stepper motor) or a solenoid (e.g.,linear solenoid, rotary solenoid). In a particular embodiment, theactuator is a rotational stepper motor with a notch that correspondswith the gear teeth of the main/star gear.

The regulating mechanism may further include one or more gears of a gearassembly. One or more of the gears may be, for example, compound gearshaving a small diameter gear attached at a shared center point to alarge diameter gear. The gear assembly may include a winch gear coupledto a winch drum/gear upon which the tether may be releasably wound.Accordingly, rotation of the gear assembly initiated by the actuator maybe coupled to winch drum/gear (i.e., through the gear assembly), therebycontrolling the distribution of tether, the rate of expansion of thebiasing members and the axial translation of the piston, and the rate ofmovement of plunger seal within barrel to force a fluid from drugchamber. The rotational movement of the winch drum/gear, and thus theaxial translation of the piston and plunger seal, are metered,restrained, or otherwise prevented from free axial translation by othercomponents of the regulating element, as described herein. Notably, theregulating mechanisms of the present disclosure do not drive thedelivery of fluid substances from the drug chamber. The delivery offluid substances from the drug chamber is caused by the expansion of thebiasing member from its initial energized state acting upon the pistonand plunger seal. The regulating mechanisms instead function to provideresistance to the free motion of the piston and plunger seal as they arepushed by the expansion of the biasing member from its initial energizedstate. The regulating mechanism does not drive the delivery but onlycontrols the delivery motion. The tether limits or otherwise restrainsthe motion of the piston and plunger seal, but does not apply the forcefor the delivery.

In addition to controlling the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer (thereby delivering drug substances at variable rates and/ordelivery profiles); the multi-function drive mechanisms of the presentdisclosure may concurrently or sequentially perform the steps of:triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a user; and connecting a sterile fluid pathway to adrug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. In at least oneembodiment, initial motion by the actuator of the multi-function drivemechanism causes rotation of main/star gear. In one manner, main/stargear conveys motion to the regulating mechanism through gear assembly.In another manner, main/star gear conveys motion to the needle insertionmechanism through gear. As gear is rotated by main/star gear, gearengages the needle insertion mechanism to initiate the fluid pathwayconnector into the user, as described in detail above. In one particularembodiment, needle insertion mechanism is a rotational needle insertionmechanism. Accordingly, gear is configured to engage a correspondinggear surface of the needle insertion mechanism. Rotation of gear causesrotation of needle insertion mechanism through the gear interactionbetween gear of the drive mechanism and corresponding gear surface ofthe needle insertion mechanism. Once suitable rotation of the needleinsertion mechanism occurs, the needle insertion mechanism may beinitiated to create the fluid pathway connector into the user, asdescribed in detail herein.

In at least one embodiment, rotation of the needle insertion mechanismin this manner may also cause a connection of a sterile fluid pathway toa drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. Ramp aspect ofneedle insertion mechanism is caused to bear upon a movable connectionhub of the sterile fluid pathway connector. As the needle insertionmechanism is rotated by the multi-function drive mechanism, ramp aspectof needle insertion mechanism bears upon and translates movableconnection hub of the sterile fluid pathway connector to facilitate afluid connection therein. In at least one embodiment, the needleinsertion mechanism may be configured such that a particular degree ofrotation enables the needle/trocar to retract as detailed above.Additionally or alternatively, such needle/trocar retraction may beconfigured to occur upon a user-activity or upon movement or function ofanother component of the drug delivery device. In at least oneembodiment, needle/trocar retraction may be configured to occur uponend-of-drug-delivery, as triggered by, for example, the regulatingmechanism and/or one or more of the status readers as described herein.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug delivery pump having ahousing and an assembly platform, upon which an activation mechanism, aninsertion mechanism, a fluid pathway connector, a power and controlsystem, and a controlled delivery drive mechanism may be mounted, saiddrive mechanism having a drive housing, a piston, and a biasing member,wherein the biasing member is initially retained in an energized stateand is configured to bear upon an interface surface of the piston. Thepiston is configured to translate substantially axially within a drugcontainer having a plunger seal and a barrel. A tether is connected atone end to the piston and at another end to a winch drum/gear of adelivery regulating mechanism, wherein the tether restrains the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The drug container may contain a drug fluid within a drug chamberfor delivery to a user. Optionally, a cover sleeve may be utilizedbetween the biasing member and the interface surface of the piston tohide the interior components of the barrel (namely, the piston and thebiasing member) from view during operation of the drive mechanism. Thetether is configured to be released from a winch drum/gear of thedelivery regulating mechanism to meter the free expansion of the biasingmember from its initial energized state and the free axial translationof the piston upon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum/gear upon which the tether may be releasably wound, rotationof the winch drum/gear releases the tether from the winch drum/gear tometer the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The metering of the tether controls therate or profile of drug delivery to a user. The piston may be one ormore parts and connects to a distal end of the tether. The winchdrum/gear is coupled to a regulating mechanism which controls rotationof the winch drum/gear and hence metering of the translation of thepiston.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch drum/gear and thereby permit axialtranslation of the piston by the biasing member to translate a plungerseal within a barrel. The one or more inputs may be provided by theactuation of the activation mechanism, a control interface, and/or aremote control mechanism. The power and control system may be configuredto receive one or more inputs to adjust the restraint provided by thetether and winch drum/gear on the free axial translation of the pistonupon which the biasing member bears upon to meet a desired drug deliveryrate or profile, to change the dose volume for delivery to the user,and/or to otherwise start, stop, or pause operation of the drivemechanism.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of the actuator. The change in the rate of movement ofthe actuator causes a change in the rotation rate of the regulatingmechanism which, in turn, controls the rate of drug delivery to theuser. Alternatively, the delivery profile may be altered by a change inthe characteristics of the flow path of medicament through the conduitconnecting the drug container and insertion mechanism. The change may becaused by the introduction, removal, or modification of a flowrestrictor which restricts flow of medicament from the drug container tothe insertion mechanism. For example, a flow restrictor may havemultiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances and drug delivery pumps whichincorporate such multi-function drive mechanisms. The multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The drive mechanisms of the present disclosurecontrol the rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container and, thus, are capableof delivering drug substances at variable rates and/or deliveryprofiles. Additionally, the drive mechanisms of the present disclosureprovide integrated status indication features which provide feedback tothe user before, during, and after drug delivery. For example, the usermay be provided an initial feedback to identify that the system isoperational and ready for drug delivery. Upon activation, the system maythen provide one or more drug delivery status indications to the user.At completion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication.

The novel devices of the present disclosure provide drive mechanismswith integrated status indication and drug delivery pumps whichincorporate such drive mechanisms. Such devices are safe and easy touse, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. The novel devices of the presentdisclosure provide these desirable features without any of the problemsassociated with known prior art devices. Certain non-limitingembodiments of the novel drug delivery pumps, drive mechanisms, andtheir respective components are described further herein with referenceto the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.69A-169 show an exemplary drug delivery device according to at least oneembodiment of the present disclosure with the top housing removed sothat the internal components are visible. The drug delivery device maybe utilized to administer delivery of a drug treatment into a body of auser. As shown in FIGS. 69A-69C, the drug delivery device 9010 includesa pump housing 9012. Pump housing 9012 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug delivery device. Forexample, drug delivery device 9010 includes a pump housing 9012 whichmay include an upper housing and a lower housing (not shown for ease ofviewing internal components). The pump housing 9012 may include one ormore tamper evidence features to identify if the drug delivery devicehas been opened or tampered with. For example, the pump housing 9012 mayinclude one or more tamper evidence labels or stickers, such as labelsthat bridge across the upper housing and the lower housing. Additionallyor alternatively, the housing 9012 may include one or more snap arms orprongs connecting between the upper housing and the lower housing. Abroken or altered tamper evidence feature would signal to the user, thephysician, the supplier, the manufacturer, or the like, that the drugdelivery device has potentially been tampered, e.g., by accessing theinternal aspects of the device, so that the device is evaluated andpossibly discarded without use by or risk to the user. The drug deliverydevice may further include an activation mechanism, a status indicator,and a window. Window may be any translucent or transmissive surfacethrough which the operation of the drug delivery device may be viewed.As shown in FIG. 69B, drug delivery device 9010 further includesassembly platform 9020, sterile fluid conduit 30, drive mechanism 90100having drug container 9050, insertion mechanism 90200, fluid pathwayconnector 90300, and a power and control system (not shown). One or moreof the components of such drug delivery devices may be modular in thatthey may be, for example, pre-assembled as separate components andconfigured into position onto the assembly platform 9020 of the drugdelivery device 9010 during manufacturing.

The pump housing 9012 contains all of the device components and providesa means of removably attaching the device 9010 to the skin of the user.The pump housing 9012 also provides protection to the interiorcomponents of the device 9010 against environmental influences. The pumphousing 9012 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9012 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9012 may include certaincomponents, such as one or more status indicators and windows, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9010 provides anactivation mechanism that is displaced by the user to trigger the startcommand to the power and control system. In a preferred embodiment, theactivation mechanism is a start button that is located through the pumphousing 9012, such as through an aperture between upper housing andlower housing, and which contacts either directly or indirectly thepower and control system. In at least one embodiment, the start buttonmay be a push button, and in other embodiments, may be an on/off switch,a toggle, or any similar activation feature known in the art. The pumphousing 9012 also provides one or more status indicators and windows. Inother embodiments, one or more of the activation mechanism, the statusindicator, the window, and combinations thereof may be provided on theupper housing or the lower housing such as, for example, on a sidevisible to the user when the drug delivery device 9010 is placed on thebody of the user. Housing 9012 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device 9010 is configured such that, upon activation by auser by depression of the activation mechanism, the multi-function drivemechanism is activated to: insert a fluid pathway into the user; enable,connect, or open necessary connections between a drug container, a fluidpathway, and a sterile fluid conduit; and force drug fluid stored in thedrug container through the fluid pathway and fluid conduit for deliveryinto a user. In at least one embodiment, such delivery of drug fluidinto a user is performed by the multi-function drive mechanism in acontrolled manner. One or more optional safety mechanisms may beutilized, for example, to prevent premature activation of the drugdelivery device. For example, an optional on-body sensor (not visible)may be provided in one embodiment as a safety feature to ensure that thepower and control system, or the activation mechanism, cannot be engagedunless the drug delivery device 9010 is in contact with the body of theuser. In one such embodiment, the on-body sensor is located on thebottom of lower housing where it may come in contact with the user'sbody. Upon displacement of the on-body sensor, depression of theactivation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor is a mechanical safety mechanism, such asfor example a mechanical lock out, that prevents triggering of the drugdelivery device 9010 by the activation mechanism. In another embodiment,the on-body sensor may be an electro-mechanical sensor such as amechanical lock out that sends a signal to the power and control systemto permit activation. In still other embodiments, the on-body sensor canbe electrically based such as, for example, a capacitive- orimpedance-based sensor which must detect tissue before permittingactivation of the power and control system. These concepts are notmutually exclusive and one or more combinations may be utilized withinthe breadth of the present disclosure to prevent, for example, prematureactivation of the drug delivery device. In a preferred embodiment, thedrug delivery device 9010 utilizes one or more mechanical on-bodysensors. Additional integrated safety mechanisms are described hereinwith reference to other components of the novel drug delivery devices.

XVI.A. Power and Control System:

The power and control system may include a power source, which providesthe energy for various electrical components within the drug deliverydevice, one or more feedback mechanisms, a microcontroller, a circuitboard, one or more conductive pads, and one or more interconnects. Othercomponents commonly used in such electrical systems may also beincluded, as would be appreciated by one having ordinary skill in theart. The one or more feedback mechanisms may include, for example,audible alarms such as piezo alarms and/or light indicators such aslight emitting diodes (LEDs). The microcontroller may be, for example, amicroprocessor. The power and control system controls several deviceinteractions with the user and interfaces with the drive mechanism90100. In one embodiment, the power and control system interfaces eitherdirectly or indirectly with the on-body sensor 9024 to identify when thedevice is in contact with the user and/or the activation mechanism toidentify when the device has been activated. The power and controlsystem may also interface with the status indicator of the pump housing9012, which may be a transmissive or translucent material which permitslight transfer, to provide visual feedback to the user. The power andcontrol system interfaces with the drive mechanism 90100 through one ormore interconnects to relay status indication, such as activation, drugdelivery, and end-of-dose, to the user. Such status indication may bepresented to the user via auditory tones, such as through the audiblealarms, and/or via visual indicators, such as through the LEDs. In apreferred embodiment, the control interfaces between the power andcontrol system and the other components of the drug delivery device arenot engaged or connected until activation by the user. This is adesirable safety feature that prevents accidental operation of the drugdelivery device and may additionally maintain the energy contained inthe power source during storage, transportation, and the like.

The power and control system may be configured to provide a number ofdifferent status indicators to the user. For example, the power andcontrol system may be configured such that after the on-body sensorand/or trigger mechanism have been pressed, the power and control systemprovides a ready-to-start status signal via the status indicator ifdevice start-up checks provide no errors. After providing theready-to-start status signal and, in an embodiment with the optionalon-body sensor, if the on-body sensor remains in contact with the bodyof the user, the power and control system will power the drive mechanism90100 to begin delivery of the drug treatment through the fluid pathwayconnector 90300 and sterile fluid conduit 9030 (not shown).

Additionally, the power and control system may be configured to identifyremoval of the drug delivery device from its packaging. The power andcontrol system may be mechanically, electronically, orelectro-mechanically connected to the packaging such that removal of thedrug delivery device from the packaging may activate or power-on thepower and control system for use, or simply enable the power and controlsystem to be powered-on by the user. In such an embodiment, withoutremoval of the drug delivery device from the packaging the drug deliverydevice cannot be activated. This provides an additional safety mechanismof the drug delivery device and for the user. In at least oneembodiment, the drug delivery device or the power and control system maybe electronically or electro-mechanically connected to the packaging,for example, such as by one or more interacting sensors from a range of:Hall effect sensors; giant magneto resistance (GMR) or magnetic fieldsensors; optical sensors; capacitive or capacitance change sensors;ultrasonic sensors; and linear travel, LVDT, linear resistive, orradiometric linear resistive sensors; and combinations thereof, whichare capable of coordinating to transmit a signal between components toidentify the location there-between. Additionally or alternatively, thedrug delivery device or the power and control system may be mechanicallyconnected to the packaging, such as by a pin and slot relationship whichactivates the system when the pin is removed (i.e., once the drugdelivery device is removed from the packaging).

In a preferred embodiment of the present disclosure, once the power andcontrol system has been activated, the multi-function drive mechanism isinitiated to actuate the insertion mechanism 90200 and the fluid pathwayconnector 90300, while also permitting the drug fluid to be forced fromthe drug container. During the drug delivery process, the power andcontrol system is configured to provide a dispensing status signal viathe status indicator. After the drug has been administered into the bodyof the user and after the end of any additional dwell time, to ensurethat substantially the entire dose has been delivered to the user, thepower and control system may provide an okay-to-remove status signal viathe status indicator. This may be independently verified by the user byviewing the drive mechanism and drug dose delivery through the window ofthe pump housing 9012. Additionally, the power and control system may beconfigured to provide one or more alert signals via the statusindicator, such as for example alerts indicative of fault or operationfailure situations.

The power and control system may additionally be configured to acceptvarious inputs from the user to dynamically control the drive mechanisms90100 to meet a desired drug delivery rate or profile. For example, thepower and control system may receive inputs, such as from partial orfull activation, depression, and/or release of the activation mechanism,to set, initiate, stop, or otherwise adjust the control of the drivemechanism 90100 via the power and control system to meet the desireddrug delivery rate or profile. Similarly, the power and control systemmay be configured to receive such inputs to adjust the drug dose volume;to prime the drive mechanism, fluid pathway connector, and fluidconduit; and/or to start, stop, or pause operation of the drivemechanism 90100. Such inputs may be received by the user directly actingon the drug delivery device 9010, such as by use of the activationmechanism 9014 or a different control interface, or the power andcontrol system may be configured to receive such inputs from a remotecontrol device. Additionally or alternatively, such inputs may bepre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism of the drugdelivery device 9010 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

XVI.B. Insertion Mechanism:

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure, including a rigid needle insertion mechanismand/or a rotational needle insertion mechanism as developed by theassignee of the present disclosure.

In at least one embodiment, the insertion mechanism 90200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 69B and FIG. 69C). The connection of the base to theassembly platform 9020 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9010. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9030 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9027 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane (not visible).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. Displacement of the lockoutpin(s), by one or more methods such as pulling, pushing, sliding, and/orrotation, permits insertion biasing member to decompress from itsinitial compressed, energized state. This decompression of the insertionbiasing member drives the needle and, optionally, the cannula into thebody of the user. At the end of the insertion stage or at the end ofdrug delivery (as triggered by the multi-function drive mechanism), theretraction biasing member is permitted to expand in the proximaldirection from its initial energized state. This axial expansion in theproximal direction of the retraction biasing member retracts the needle.If an inserter needle/trocar and cannula configuration are utilized,retraction of the needle may occur while maintaining the cannula influid communication with the body of the user. Accordingly, theinsertion mechanism may be used to insert a needle and cannula into theuser and, subsequently, retract the needle while retaining the cannulain position for drug delivery to the body of the user.

In at least one embodiment, as shown in FIG. 75, the insertion mechanismincludes a rotationally biased member 90210 which is initially held inan energized state. In a preferred embodiment, the rotationally biasedmember is a torsional spring. The rotational biasing member may beprevented from de-energizing by interaction of gear surface 90208 withgear 90112 or, alternatively, by contact of a component of the insertionmechanism with a rotation prevention feature of the drug deliverydevice. Upon activation of the device, or another input, therotationally biased member 90210 is permitted to, at least partially,de-energize. This causes one or more components of the insertionmechanism to rotate and, in turn, cause, or allow, the insertion of theneedle into the patient. Further, a cannula may be inserted into thepatient as described above. At a later time, such as when the controlarm or another component of the device recognizes a slack in the tether,the rotationally biased member may be allowed to further de-energize,causing additional rotation of one or more components of the insertionmechanism. This rotation may cause, or allow, the needle to be retractedfrom the patient. The needle may be fully retracted in a single step orthere may be multiple steps of retraction.

XVI.C. Fluid Pathway Connector:

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9010, the fluid pathway connector 90300 isenabled to connect the sterile fluid conduit 9030 to the drug containerof the drive mechanism 90100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 90100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user. In one such embodiment, the fluid pathway connector may besubstantially similar to that described in International PatentApplication No. PCT/US2012/054861, which is included by reference hereinin its entirety for all purposes. In such an embodiment, a compressiblesterile sleeve may be fixedly attached between the cap of the drugcontainer and the connection hub of the fluid pathway connector. Thepiercing member may reside within the sterile sleeve until a connectionbetween the fluid connection pathway and the drug container is desired.The sterile sleeve may be sterilized to ensure the sterility of thepiercing member and the fluid pathway prior to activation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Applications No.PCT/US2013/030478 or No. PCT/US2014/052329, for example, which areincluded by reference herein in their entirety for all purposes.According to such an embodiment, a drug container may have a drugchamber within a barrel between a pierceable seal and a plunger seal. Adrug fluid is contained in the drug chamber. Upon activation of thedevice by the user, a drive mechanism asserts a force on a plunger sealcontained in the drug container. As the plunger seal asserts a force onthe drug fluid and any air/gas gap or bubble, a combination of pneumaticand hydraulic pressure builds by compression of the air/gas and drugfluid and the force is relayed to the sliding pierceable seal. Thepierceable seal is caused to slide towards the cap, causing it to bepierced by the piercing member retained within the integrated sterilefluid pathway connector. Accordingly, the integrated sterile fluidpathway connector is connected (i.e., the fluid pathway is opened) bythe combination pneumatic/hydraulic force of the air/gas and drug fluidwithin the drug chamber created by activation of a drive mechanism. Oncethe integrated sterile fluid pathway connector is connected or opened,drug fluid is permitted to flow from the drug container, through theintegrated sterile fluid pathway connector, sterile fluid conduit, andinsertion mechanism, and into the body of the user for drug delivery. Inat least one embodiment, the fluid flows through only a manifold and acannula and/or needle of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery.

In a preferred embodiment, the sterile fluid pathway connector isinitiated by movement of the needle insertion mechanism, which itself isinitiated by the multi-function drive mechanism. Additionally oralternatively, the sterile fluid pathway connector is initiated bymovement directly of the multi-function drive mechanism. For example,the multi-function drive mechanism may include a rotational gear, suchas the star gear described in detail herein, that acts concurrently orsequentially to control the rate of drug delivery, to actuate the needleinsertion mechanism, and/or initiate the sterile fluid pathwayconnector. In one particular embodiment, shown in FIGS. 69A-69C, themulti-function drive mechanism performs all of these steps substantiallyconcurrently. The multi-function drive mechanism rotates a gear thatacts upon several other components. The gear acts on a gear assembly tocontrol the rate of drug delivery, while also contacting a needleinsertion mechanism to introduce a fluid pathway into the user. As theneedle insertion mechanism is initiated, the sterile fluid connection ismade to permit drug fluid flow from the drug container, through thefluid conduit, into the needle insertion mechanism, for delivery intothe patient as the gear and gear assembly of the multi-function drivemechanism control the rate of drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 300 and the sterile fluid conduit 30 are providedhereinafter in later sections in reference to other embodiments.

XVI.D. Multi-Function Drive Mechanism:

The multi-function drive mechanisms of the present disclosure enable orinitiate several functions, including: (i) controlling the rate of drugdelivery by metering, providing resistance, or otherwise preventing freeaxial translation of the plunger seal utilized to force a drug substanceout of a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. With reference to the embodiments shown in FIGS.70A-70D and 3A-3D, multi-function drive mechanism 90100 includes anactuator 90101, a gear assembly 90110 including a main gear 90102, adrive housing 90130, and a drug container 9050 having a cap 9052, apierceable seal (not visible), a barrel 9058, and a plunger seal 9060.The main gear 90102 may be, for example, a star gear disposed to contactmultiple secondary gears or gear surfaces. A drug chamber 9021, locatedwithin the barrel 9058 between the pierceable seal and the plunger seal9060, may contain a drug fluid for delivery through the insertionmechanism and drug delivery device into the body of the user. The sealsdescribed herein may be comprised of a number of materials but are, in apreferred embodiment, comprised of one or more elastomers or rubbers.The drive mechanism 90100 may further contain one or more drive biasingmembers, one or more release mechanisms, and one or more guides, as aredescribed further herein. The components of the drive mechanism functionto force a fluid from the drug container out through the pierceableseal, or preferably through the piercing member of the fluid pathwayconnector, for delivery through the fluid pathway connector, sterilefluid conduit, and insertion mechanism into the body of the user.

In one particular embodiment, the drive mechanism 90100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. The fluid pathway connector may beconnected through the pierceable seal prior to, concurrently with, orafter activation of the drive mechanism to permit fluid flow from thedrug container, through the fluid pathway connector, sterile fluidconduit, and insertion mechanism, and into the body of the user for drugdelivery. In at least one embodiment, the fluid flows through only amanifold and a cannula of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detail herein.

Referring now to the embodiment of the multi-function drive mechanismshown in FIGS. 70A-70D and 71A-71D, multi-function drive mechanism 90100includes an actuator 90101, a gear assembly 90110 including a main gear90102, a drive housing 90130, and a drug container 9050 having a cap9052, a pierceable seal (not visible), a barrel 9058, and a plunger seal9060. The main gear 90102 may be, for example, a star gear disposed tocontact multiple secondary gears or gear surfaces. A drug chamber 9021,located within the barrel 9058 between the pierceable seal and theplunger seal 9060, may contain a drug fluid for delivery through theinsertion mechanism and drug delivery device into the body of the user.Compressed within the drive housing 90130, between the drug container9050 and the proximal end of the housing 90130, are one or more drivebiasing members 90122 and a piston 90110, wherein the drive biasingmembers 90122 are configured to bear upon an interface surface 90110C ofthe piston 90110, as described further herein. Optionally, a coversleeve (not shown) may be utilized between the drive biasing members90122 and the interface surface 90110C of the piston 90110 to, forexample, promote more even distribution of force from the drive biasingmember 90122 to the piston 90110, prevent buckling of the drive biasingmembers 90122, and/or hide biasing members 90122 from user view.Interface surface 90110C of piston 90110 is caused to rest substantiallyadjacent to, or in contact with, a proximal end of seal 9060. Althoughthe embodiments shown in FIGS. 70A-70D and 71A-71D show a singularbiasing member it is also contemplated that one or more biasing membersdisposed to act in parallel may be used.

As best shown in FIG. 70D and FIG. 71D, the piston 90110 may becomprised of two components 90110A and 90110B and have an interfacesurface 90110C to contact the plunger seal. A tether, ribbon, string, orother retention strap (referred to herein as the “tether” 90525) may beconnected at one end to the piston 90110A, 90110B. For example, thetether 90525 may be connected to the piston 90110A, 90110B by retentionbetween the two components of the piston 90110A, 90110B when assembled.The tether 90525 is connected at another end to a winch drum/gear 90520of a delivery control mechanism 90500. Through the use of the winchdrum/gear 90520 connected to one end of the tether 90525, and the tether90525 connected at another end to the piston 90110A, 90110B, theregulating mechanism 90500 functions to control, meter, provideresistance, or otherwise prevent free axial translation of the piston90110A, 90110B and plunger seal 9060 utilized to force a drug substanceout of a drug container 9050. Accordingly, the regulating mechanism90500 is a portion of the gear assembly 90116 aspect of themulti-function drive mechanism, which together function to control therate or profile of drug delivery to the user.

As shown in FIGS. 70A-70D and 71A-71D, and in isolation in FIGS. 72 and73A-73B, in the embodiments of the present disclosure, the regulatingmechanism 90500 is gear assembly driven by an actuator 90101 of themulti-function drive mechanism 90100. The regulating mechanism retardsor restrains the distribution of tether 90525, only allowing it toadvance at a regulated or desired rate. This restricts movement ofpiston 90110 within barrel 9058, which is pushed by one or more biasingmembers 90122, hence controlling the movement of plunger seal 9060 anddelivery of the drug contained in chamber 9021. As the plunger seal 9060advances in the drug container 9050, the drug substance is dispensedthrough the sterile pathway connection 90300, conduit 9030, insertionmechanism 90200, and into the body of the user for drug delivery. Theactuator 90101 may be a number of power/motion sources including, forexample, a solenoid, a stepper motor, or a rotational drive motor. In aparticular embodiment, the actuator 90101 is a rotational stepper motorwith a notch that corresponds with the gear teeth of the main/star gear90102. Commonly, such a rotational stepper motor may be referred to as a‘Pac-Man’ motor. In at least one embodiment, the Pac-Man motor has agear interface within which one or more teeth of the main gear maypartially reside during operation of the system. This is more clearlyvisible in FIGS. 73A-73B. When the gear interface 90101A of the Pac-Manmotor 90101 is in alignment with a tooth 90102A of the main gear 90102,rotational motion of the Pac-Man motor 90101 causes gear interfacerotation of the main gear 90102. When the Pac-Man motor 90101 is betweengear teeth of the main gear, it may act as a resistance for, forexample, back-spinning or unwinding of the gear assembly 90116. In oneparticular embodiment, the Pac-Man motor 90101 utilizes an alternatingdirection type motor to rotate the Pac-Man motor 90101 backwards andforwards. This configuration aids in the prevention of a runawaycondition, where the motor and the gears are freely permitted to rotate,by using the multi-direction of the motor to prevent continuous spin inone direction (as would be needed for a runaway condition). Thisbi-directional movement of the motor, coupled with the use of the gearinterface cut within the Pac-Man motor, provide suitable safety featuresto prevent a runaway condition that could potentially lead toover-delivery of drug to the user. Further detail about the gearassembly 90116, regulating mechanism 90500, and multi-function drivemechanism 90100 are provided herein.

In a particular embodiment shown in FIGS. 73A-73B, the regulatingelement 90500 further includes one or more gears 90511, 90512, 90513,90514, of a gear assembly 90516. One or more of the gears 90511, 90512,90513, 90514 may be, for example, compound gears having a small diametergear attached at a shared center point to a large diameter gear. Gear90513 may be rotationally coupled to winch drum/gear 90520, for exampleby a keyed shaft, thereby coupling rotation of gear assembly 90516 towinch drum/gear 90520. Compound gear 90512 engages the small diametergear 90513 such that rotational movement of the compound gear aspect90512B is conveyed by engagement of the gears (such as by engagement ofcorresponding gear teeth) to gear 90513. Compound gear aspect 90512A,the rotation of which is coupled to gear aspect 90512B, is caused torotate by action of compound gear aspect 90102B of the main/star gear90102. Compound gear aspect 90102B, the rotation of which is coupled tomain/star gear 90102, is caused to rotate by interaction betweenmain/star gear 90102A and interface 90101A of the actuator 90101. Thus,rotation of main/star gear 90102 is conveyed to winch drum/gear 90520.Accordingly, rotation of the gear assembly 90516 initiated by theactuator 90101 may be coupled to winch drum/gear 90520 (i.e., throughthe gear assembly 90516), thereby controlling the distribution of tether90525, and the rate of movement of plunger seal 9060 within barrel 9058to force a fluid from drug chamber 9021. The rotational movement of thewinch drum/gear 90520, and thus the axial translation of the piston90110 and plunger seal 9060, are metered, restrained, or otherwiseprevented from free axial translation by other components of theregulating element 90500, as described herein. As described above, theactuator 90101 may be a number of known power/motion sources including,for example, a motor (e.g., a DC motor, AC motor, or stepper motor) or asolenoid (e.g., linear solenoid, rotary solenoid).

The embodiment described above and shown in FIGS. 69A-73D show anactuator 90101 that is in vertical alignment and in direct engagementwith the main/star gear 90102. As would readily be appreciated by onehaving ordinary skill in the mechanical arts, the actuator 90101 couldbe modified to be in horizontal alignment. Additionally oralternatively, the actuator 90101 could be modified to be in indirectengagement with the main/star gear 90102. The embodiments shown in FIGS.75A-75B show an actuator 90101 that is in horizontal alignment andindirect engagement with the main/star gear 90102. Such an embodimentmay utilize a rack and pinion engagement, a drive screw, or a worm gear101W, as shown in FIGS. 5A-75B, to change the direction of motion fromhorizontal to vertical (i.e., perpendicular interaction). Actuator 90101rotates worm gear 90101W, which engages gear 90101G and conveys themotion to the Pac-Man gear 90101A. The Pac-Man gear 90101A engagesmain/star gear 90102 to enable operation of the drive mechanism and thedrug delivery device, as described herein. Main/star gear 90102 alsodrives operation of gear 90112 to enable operation of the needleinsertion mechanism 90200, as described herein. In one particularembodiment, the actuator 90101 utilizes an alternating direction typemotor to rotate the worm gear 90101W, gear 90101G, and Pac-Man gear90101A backwards and forwards. This configuration aids in the preventionof a runaway condition, where the motor and the gears are freelypermitted to rotate, by using the multi-direction of the motor toprevent continuous spin in one direction (as would be needed for arunaway condition). This bi-directional movement of the actuator 90101,coupled with the use of the gear interface of the worm gear 90101W, gear90101G, and Pac-Man gear 90101A with the main/star gear 90102, providesuitable safety features to prevent a runaway condition that couldpotentially lead to over-delivery of drug to the user. Additionally, theactuator 90101 may include a stop member 90101B that stops the rotationof the Pac-Man gear 90101A against a stop block 90150. Stop block 90150further prevents over-rotation of the Pac-Man gear 90101A and,accordingly, the main/star gear 90102 to prevent a runaway conditionthat could potentially lead to over-delivery of drug to the user. Forthe device to function in this configuration, the Pac-Man gear 90101Amust be rotated backwards the other direction before rotating forwardsagain to progress the main/star gear 90102 because the stop member90101B prevents over rotation in one direction by interaction with thestop block 90150. Additionally, the geometry of worm gear 90101W may beconfigured such that it is self-locking and/or cannot be back-driven bygear 90101G. This may be done by configuration of parameters such as:pitch, lead angle, pressure angle, and number of threads. In so doing,runaway conditions of the drive mechanism will be prevented by the wormgear's resistance to rotations that are not caused by actuator 90101.

Notably, the regulating mechanisms 90500 of the present disclosure donot drive the delivery of fluid substances from the drug chamber 9021.The delivery of fluid substances from the drug chamber 9021 is caused bythe expansion of the biasing member 90122 from its initial energizedstate acting upon the piston 90110A, 90110B and plunger seal 9060. Theregulating mechanisms 90500 instead function to provide resistance tothe free motion of the piston 90110A, 90110B and plunger seal 9060 asthey are pushed by the expansion of the biasing member 90122 from itsinitial energized state. The regulating mechanism 90500 does not drivethe delivery but only controls the delivery motion. The tether limits orotherwise restrains the motion of the piston 90110 and plunger seal9060, but does not apply the force for the delivery. According to apreferred embodiment, the controlled delivery drive mechanisms and drugdelivery devices of the present disclosure include a regulatingmechanism indirectly or directly connected to a tether metering theaxial translation of the piston 90110A, 90110B and plunger seal 9060,which are being driven to axially translate by the biasing member 90122.The rate of drug delivery as controlled by the regulating mechanism maybe determined by: selection of the gear ratio of gear assembly 90516;selection of the main/star gear 90102; selection of the diameter ofwinding drum/gear 90520; using electromechanical actuator 90101 tocontrol the rate of rotation of the main/star gear 90102; or any othermethod known to one skilled in the art. By using electromechanicalactuator 90101 the rate of rotation of the main/star gear 90102 it maybe possible to configure a drug delivery device to provide a variabledose rate (i.e., the rate of drug delivery is varied during atreatment).

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether 90525 by the winch drum/gear 90520 and thereby permitaxial translation of the piston 90110 by the biasing member 90122 totranslate a plunger seal 9060 within a barrel 9058. The one or moreinputs may be provided by the actuation of the activation mechanism, acontrol interface, and/or a remote control mechanism. The power andcontrol system may be configured to receive one or more inputs to adjustthe restraint provided by the tether 90525 and winch drum/gear 90520 onthe free axial translation of the piston 90110 upon which the biasingmember 90122 bears upon to meet a desired drug delivery rate or profile,to change the dose volume for delivery to the user, and/or to otherwisestart, stop, or pause operation of the drive mechanism.

The components of the drive mechanism 90100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 60 of the drug container 9050. Optionally, the drive mechanism90100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9060 to, for example,ensure that substantially the entire drug dose has been delivered to theuser. For example, the plunger seal 9060, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user.

The tether 90525 may have one or more status triggers, such aselectrical contacts, optical markings, or electromechanical pins orrecesses, which are capable of contacting or being recognized by astatus reader. In at least one embodiment, an end-of-dose statusindication may be provided to the user once the status reader contactsor recognizes the final status trigger positioned on the tether 90525that would contact the status reader at the end of axial travel of thepiston 90110A, 90110B and plunger 9060 within the barrel 9058 of thedrug container 9050. The status reader may be, for example, anelectrical switch reader to contact the corresponding electricalcontacts, an optical reader to recognize the corresponding opticalmarkings, or a mechanical or electromechanical reader configured tocontact corresponding pins, holes, or similar aspects on the tether. Thestatus triggers may be positioned along the tether 90525 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asthe drug delivery device is activated and drug delivery is begun byrelease of the biasing member 90122 and the resulting force applied tothe piston 90110A, 90110B and plunger seal 9060, the rate or profile ofdrug delivery to the user is controlled by the regulating mechanism90500, gear assembly 90516, and winch drum/gear 90520 releasing thetether 90525 and permitting expansion of the biasing member 90122 andaxial translation of the piston 90110A, 90110B and plunger seal 9060. Asthis occurs, the status triggers of the tether 90525 are contacted orrecognized by the status reader and the status of the drive mechanismbefore, during, and after operation can be relayed to the power andcontrol system to provide feedback to the user. Depending on the numberof status triggers located on the tether 90525, the frequency of theincremental status indication may be varied as desired. As describedabove, a range of status readers may be utilized depending on the statustriggers utilized by the system.

In a preferred embodiment, the status reader may apply a tensioningforce to the tether 90525. When the system reaches end-of-dose, thetether 90525 goes slack and the status reader 90544 is permitted torotate about a fulcrum. This rotation may operate an electrical orelectromechanical switch, for example a switch, signaling slack in thetether 90525 to the power and control system. Additionally, a gear 90511of gear assembly 90516 may act as an encoder along with a sensor. Thesensor/encoder combination is used to provide feedback of gear assemblyrotation, which in turn can be calibrated to the position of piston90110 when there is no slack in the tether 90525. Together, the statusreader and sensor/encoder may provide positional feedback, end-of-dosesignal, and error indication, such as an occlusion, by observing slackin the tether 90525 prior to reaching the expected number of motorrotations as counted by the sensor/encoder.

Additional means may exist for terminating or restraining the flow ofthe medicament in the case of slack in, or failure of, the tether. FIGS.6A-6B show one such embodiment. Disposed within barrel 9058 are brake9064, sleeve 9062, and plug 9068, and optionally retainer 66. Biasingmember 90122 bears against sleeve 9062. Tether 90525 is engaged withplug 9068, thereby allowing tether 90525 to restrain the motion ofsleeve 9062. This restraint controls the rate of expansion orde-energizing of biasing member 90122. When tether 90525 is undertension, plug 9068 bears against distal face 9064A of brake 9064,causing proximal face 9064B of brake 9064 to bear against sleeve 9062.Due to this contact, and the profile of the distal end 9062A of sleeve9062, brake 9064 is maintained in a substantially conical configurationas shown in FIG. 6A. In this configuration, expansion or de-energizingof biasing member 90122 is restrained. Also, in this conicalconfiguration, the outer diameter of brake 64 is less than the innerdiameter of barrel 9058, thus translation of the brake is not restrainedby contact with the inner wall of the drug container. Also, a portion ofbrake 9064 is in contact with retainer 9066. Because brake 9064 ismaintained in this configuration by plug 9068 and sleeve 9062,translation of sleeve 9062, caused by decompression of biasing member90122, is transferred to retainer 9066. Likewise, contact of retainer9066 with plunger seal 9060 causes translation of plunger seal 9060.

As shown in FIG. 74B, in the event of slack in, or failure of, tether90525, plug 9068 is no longer held in position by tether 90525 and,therefore, no longer restrains motion of sleeve 9062. As biasing member90122 decompresses or de-energizes, brake 9064 transforms to arelatively less conical or flatter configuration. This may be caused bya natural bias of brake 9064 to transform to this configuration or,alternatively, may be caused by contact of brake 9064 with both retainer9066 and sleeve 9062. As the brake is transformed, it comes into contactwith the inner wall of barrel 9058. The brake thus acts as a wedge torestrict translation of sleeve 9062. This may prevent furthertranslation or may act to restrict the rate of translation. Optionally,restoring tension in the tether may cause the plug to contact the brakeand to transform the brake back to its conical configuration and thusrestore normal operation of the drug delivery device.

FIGS. 74A-74B show the plug as having a spherical shape and the brake ashaving a conical shape. Such shapes are used herein merely for exemplarypurposes and other shapes or configurations could readily be utilized toachieve the same or similar functionality. For example, the plug mayitself be conical in shape and, in one embodiment, be shaped tointerface the brake when the brake is in a conical shape. In such aconfiguration, the conical shape of the plug assists in maintaining theconical shape of the brake, thereby preventing contact between the outerdiameter of the brake with the inner diameter of the barrel in order torestrict the axial translation of the sleeve 9062 (i.e., applying abraking force). In another embodiment, the brake 9064 could employ astar-shaped or other configuration when in a substantially flattenedposition so as to make contact with the inner diameter of the barrel9058 to prevent or restrict further axial translation of sleeve 9062.Without further translation of sleeve 9062, biasing member 90122 cannotexpand or de-energize further which, in turn, prevents or restrictsfurther drug delivery to the user. This provides a necessary and usefulsafety measure for drug delivery, to prevent over-delivery oraccelerated delivery of drug to the user.

Referring back to FIGS. 70A-70D and 71A-71D, in addition to controllingthe rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container (thereby deliveringdrug substances at variable rates and/or delivery profiles); themulti-function drive mechanisms of the present disclosure mayconcurrently or sequentially perform the steps of: triggering a needleinsertion mechanism to provide a fluid pathway for drug delivery to auser; and connecting a sterile fluid pathway to a drug container topermit fluid flow from the drug container to the needle insertionmechanism for delivery to the user. In at least one embodiment, as shownin FIGS. 70A-70D and 71A-71D, initial motion by the actuator 90101 ofthe multi-function drive mechanism 90100 causes rotation of main/stargear 90102. Main/star gear 90102 is shown as a compound gear withaspects 90102A and 90102B (see FIG. 72). In one manner, main/star gear90102 conveys motion to the regulating mechanism 90500 through gearassembly 90516. In another manner, main/star gear 90102 conveys motionto the needle insertion mechanism 90200 through gear 90112. As gear90112 is rotated by main/star gear 90102, gear 90112 engages the needleinsertion mechanism 90200 to initiate the fluid pathway connector intothe user, as described in detail above. In one particular embodiment,needle insertion mechanism 90200 is a rotational needle insertionmechanism. Accordingly, gear 90112 is configured to engage acorresponding gear surface 90208 of the needle insertion mechanism90200. Rotation of gear 90112 causes rotation of needle insertionmechanism 90200 through the gear interaction between gear 90112 of thedrive mechanism 90100 and corresponding gear surface 90208 of the needleinsertion mechanism 90200. Once suitable rotation of the needleinsertion mechanism 90200 occurs, for example rotation along axis ‘R’shown in FIG. 70B-70C, the needle insertion mechanism may be initiatedto create the fluid pathway connector into the user, as described indetail above. In an alternative embodiment, as shown in FIGS. 75A-75B,gear 90112 may indirectly engage the needle insertion mechanism 90200 toinitiate the fluid pathway connector into the user. For example, gear90112 may be configured to engage a corresponding gear surface of acontrol arm 90202 (visible in FIG. 75) that contacts or blocks theneedle insertion mechanism 90200. Rotation of gear 90112 causes movementof the control arm 90202, which may initiate or permit rotation ofneedle insertion mechanism 90200. Such a needle insertion mechanism, asshown in FIGS. 75A-75B, includes a rotationally biased member 90210which is initially held in an energized state. The rotational biasingmember may be prevented from de-energizing by contact of a component ofthe insertion mechanism with a rotation prevention feature, such as ablocking aspect of the control arm, of the drug delivery device. Uponactivation of the device, or another input, the rotationally biasedmember 90210 is permitted to, at least partially, de-energize. Thiscauses one or more components of the insertion mechanism to rotate and,in turn, cause, or allow, the insertion of the needle into the patient.Further, a cannula may be inserted into the patient as described above.At a later time, such as when the control arm or another component ofthe device recognizes a slack in the tether 90525, the rotationallybiased member may be allowed to further de-energize, such as by furtherinteraction with the control arm, causing additional rotation of one ormore components of the insertion mechanism. This rotation may cause, orallow, the needle to be retracted from the patient. The needle may befully retracted in a single step or there may be multiple steps ofretraction.

As shown in FIGS. 70A-70D and 71A-71D, rotation of the needle insertionmechanism 90200 in this manner may also cause a connection of a sterilefluid pathway to a drug container to permit fluid flow from the drugcontainer to the needle insertion mechanism for delivery to the user.Ramp aspect 90222 of needle insertion mechanism 90200 is caused to bearupon a movable connection hub 90322 of the sterile fluid pathwayconnector 90300. As the needle insertion mechanism 90200 is rotated bythe multi-function drive mechanism 90100, ramp aspect 90222 of needleinsertion mechanism 90200 bears upon and translates movable connectionhub 90322 of the sterile fluid pathway connector 90300 to facilitate afluid connection therein. Such translation may occur, for example, inthe direction of the hollow arrow along axis ‘C’ shown in FIGS. 70B and71B. In at least one embodiment, the needle insertion mechanism 90200may be configured such that a particular degree of rotation uponrotational axis ‘R’ (shown in FIGS. 70B-70C) enables the needle/trocarto retract as detailed above. Additionally or alternatively, suchneedle/trocar retraction may be configured to occur upon a user-activityor upon movement or function of another component of the drug deliverydevice. In at least one embodiment, needle/trocar retraction may beconfigured to occur upon end-of-drug-delivery, as triggered by, forexample, the regulating mechanism 90500 and/or one or more of the statusreaders as described above. During these stages of operation, deliveryof fluid substances from the drug chamber 9021 may be initiated,on-going, and/or completed by the expansion of the biasing member 90122from its initial energized state acting upon the piston 90110A, 90110Band plunger seal 9060. As described above, the regulating mechanisms90500 function to provide resistance to the free motion of the piston90110A, 90110B and plunger seal 9060 as they are pushed by the expansionof the biasing member 90122 from its initial energized state. Theregulating mechanism 90500 does not drive the delivery but only controlsthe delivery motion. The tether limits or otherwise restrains the motionof the piston 90110 and plunger seal 9060, but does not apply the forcefor the delivery. This is visible through the progression of thecomponents shown in FIGS. 70A-70D and 71A-71D. The motion of the piston90110A, 90110B and plunger seal 9060 as they are pushed by the expansionof the biasing member 90122 from its initial energized state are shownin the direction of the solid arrow along axis ‘A’ from proximal orfirst position ‘P’ to the distal or second position ‘D’, as shown in thetransition of FIGS. 70A-70D and 71A-71D.

Further aspects of the novel drive mechanism will be described withreference to FIG. 72 and FIGS. 73A-73B. FIG. 72 shows a perspective viewof the multi-function drive mechanism, according to at least a firstembodiment, during its initial locked stage. Initially, the tether 90525may retain the biasing member 90122 in an initial energized positionwithin piston 90110A, 90110B. Directly or indirectly upon activation ofthe device by the user, the multi-function drive mechanism 90100 may beactivated to permit the biasing member to impart a force to piston 90110and therefore to tether 90525. This force on tether 90525 imparts atorque on winding drum 90520 which causes the gear assembly 90516 andregulating mechanism 90500 to begin motion. As shown in FIG. 73A, thepiston 90110 and biasing member 90122 are both initially in acompressed, energized state behind the plunger seal 9060. The biasingmember 90122 may be maintained in this state until activation of thedevice between internal features of drive housing 90130 and interfacesurface 90110C of piston 90110A, 90110B. As the drug delivery device9010 is activated and the drive mechanism 90100 is triggered to operate,biasing member 90122 is permitted to expand (i.e., decompress) axiallyin the distal direction (i.e., in the direction of the solid arrow shownin FIGS. 70A-70D and FIGS. 71A-71D). Such expansion causes the biasingmember 90122 to act upon and distally translate interface surface 90110Cand piston 90110, thereby distally translating plunger seal 9060 to pushdrug fluid out of the drug chamber 9021 of barrel 9058. In at least oneembodiment, an end-of-dose status indication may be provided to the useronce the status reader contacts or recognizes a status triggerpositioned on the tether 90525 to substantially correspond with the endof axial travel of the piston 90110A, 90110B and plunger seal 9060within the barrel 9058 of the drug container 9050. The status triggersmay be positioned along the tether 90525 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the user. In at least one embodiment,the status reader is an optical status reader configured to recognizethe corresponding optical status triggers on the tether. As would beunderstood by an ordinarily skilled artisan, such optical statustriggers may be markings which are recognizable by the optical statusreader. In another embodiment, the status reader is a mechanical orelectromechanical reader configured to physically contact correspondingpins, holes, or similar aspects on the tether. Electrical contacts couldsimilarly be utilized on the tether as status indicators which contactor are otherwise recognized by the corresponding electrical statusreader. The status triggers may be positioned along the tether 90525 tobe read or recognized at positions which correspond with the beginningand end of drug delivery, as well as at desired increments during drugdelivery. As shown, tether 90525 passes substantially axially throughthe drive mechanism housing 90130, the biasing member 90122, andconnects to the piston 90110 A, 90110B to restrict the axial translationof the piston 90110A, 90110B and the plunger seal 9060 that residesadjacent thereto.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement ofwinding drum 90520 and, thus, axial translation of the components of thecontrolled delivery drive mechanism 90100. Accordingly, the regulatingmechanism 90500 only controls the motion of the drive mechanism, butdoes not apply the force for the drug delivery. One or more additionalbiasing members 90122, such as compression springs, may be utilized todrive or assist the driving of the piston 90110. For example, acompression spring may be utilized within the drive housing 90130 forthis purpose. The regulating mechanism 500 only controls, meters, orregulates such action. The controlled delivery drive mechanisms and/ordrug delivery devices of the present disclosure may additionally enablea compliance push to ensure that substantially all of the drug substancehas been pushed out of the drug chamber 9021. The plunger seal 9060,itself, may have some compressibility permitting a compliance push ofdrug fluid from the drug container. For example, when a pop-out plungerseal is employed, i.e., a plunger seal that is deformable from aninitial state, the plunger seal may be caused to deform or “pop-out” toprovide a compliance push of drug fluid from the drug container.Additionally or alternatively, an electromechanical status switch andinterconnect assembly may be utilized to contact, connect, or otherwiseenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

In at least one embodiment, incremental status indication may beprovided to the user by reading or recognizing the rotational movementof one or more gears of gear assembly 90516. As the gear assembly 90516rotates, a status reader may read or recognize one or more correspondingstatus triggers on one of the gears in the gear assembly to provideincremental status indication before, during, and after operation of thevariable rate controlled delivery drive mechanism. A number of statusreaders may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism may utilize a mechanicalstatus reader which is physically contacted by gear teeth of one of thegears of the gear assembly. As the status reader is contacted by thestatus trigger(s), which in this exemplary embodiment may be the gearteeth of one of the gears (or holes, pins, ridges, markings, electricalcontacts, or the like, upon the gear), the status reader measures therotational position of the gear and transmits a signal to the power andcontrol system for status indication to the user. Additionally oralternatively, the drive mechanism may utilize an optical status reader.The optical status reader may be, for example, a light beam that iscapable of recognizing a motion and transmitting a signal to the powerand control system. For example, the drive mechanism may utilize anoptical status reader that is configured to recognize motion of the gearteeth of one of the gears in the gear assembly (or holes, pins, ridges,markings, electrical contacts, or the like, upon the gear). Similarly,the status reader may be an electrical switch configured to recognizeelectrical contacts on the gear. In any of these embodiments, the sensormay be utilized to then relay a signal to the power and control systemto provide feedback to the user.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to the user.While the drive mechanisms of the present disclosure are described withreference to the gear assembly and regulating mechanism shown in thefigures, a range of configurations may be acceptable and capable ofbeing employed within the embodiments of the present disclosure, aswould readily be appreciated by an ordinarily skilled artisan.Accordingly, the embodiments of the present disclosure are not limitedto the specific gear assembly and regulating mechanism described herein,which is provided as an exemplary embodiment of such mechanisms foremployment within the controlled delivery drive mechanisms and drugdelivery pumps.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of actuator 90101. The change in the rate of movementof actuator 90101 causes a change in the rotation rate of regulatingmechanism 90500 which, in turn, controls the rate of drug delivery tothe user. Alternatively, the delivery profile may be altered by a changein the characteristics of the flow path of medicament through theconduit connecting the drug container and insertion mechanism. Thechange may be caused by the introduction, removal, or modification of aflow restrictor which restricts flow of medicament from the drugcontainer to the insertion mechanism. For example, a flow restrictor mayhave multiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

Assembly and/or manufacturing of controlled delivery drive mechanism90100, drug delivery pump 9010, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9050 may first be assembledand filled with a fluid for delivery to the user. The drug container9050 includes a cap 9052, a pierceable seal 9056, a barrel 9058, and aplunger seal 9060. The pierceable seal 56 may be fixedly engaged betweenthe cap 9052 and the barrel 9058, at a distal end of the barrel 9058.The barrel 9058 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9060 from theproximal end of the barrel 9058. An optional connection mount 9054 maybe mounted to a distal end of the pierceable seal 9056. The connectionmount 9054 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9058 of the drug container 9050. Thedrug container 9050 may then be mounted to a distal end of drive housing90130.

One or more drive biasing members 90122 may be inserted into a distalend of the drive housing 90130. Optionally, a cover sleeve 90140 may beinserted into a distal end of the drive housing 90130 to substantiallycover biasing member 90122. A piston may be inserted into the distal endof the drive housing 90130 such that it resides at least partiallywithin an axial pass-through of the biasing member 90122 and the biasingmember 90122 is permitted to contact a piston interface surface 90110Cof piston 90110A, 90110B at the distal end of the biasing member 90122.An optional cover sleeve 90140 may be utilized to enclose the biasingmember 90122 and contact the piston interface surface 90110C of piston90110A, 90110B. The piston 90110A, 90110B and drive biasing member90122, and optional cover sleeve 90140, may be compressed into drivehousing 90130. Such assembly positions the drive biasing member 90122 inan initial compressed, energized state and preferably places a pistoninterface surface 90110C in contact with the proximal surface of theplunger seal 9060 within the proximal end of barrel 9058. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 90130 prior to attachment or mounting of the drug container9050. The tether 90525 is pre-connected to the proximal end of thepiston 90110A, 90110B and passed through the axial aperture of thebiasing member 90122 and drive mechanism 90130, and then wound throughthe interior of the drug delivery device with the other end of thetether 90525 wrapped around the winch drum/gear 90520 of the regulatingmechanism 90500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 69B.

Certain optional standard components or variations of drive mechanism90100 or drug delivery device 9010 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9018 to enablethe user to view the operation of the drug delivery device 9010 orverify that drug dose has completed. Similarly, the drug delivery device9010 may contain an adhesive patch 9026 and a patch liner 9028 on thebottom surface of the housing 9012. The adhesive patch 9026 may beutilized to adhere the drug delivery device 9010 to the body of the userfor delivery of the drug dose. As would be readily understood by onehaving ordinary skill in the art, the adhesive patch 9026 may have anadhesive surface for adhesion of the drug delivery device to the body ofthe user. The adhesive surface of the adhesive patch 9026 may initiallybe covered by a non-adhesive patch liner 9028, which is removed from theadhesive patch 9026 prior to placement of the drug delivery device 9010in contact with the body of the user. Removal of the patch liner 9028may further remove the sealing membrane 90254 of the insertion mechanism90200, opening the insertion mechanism to the body of the user for drugdelivery (as shown in FIG. 69C).

Similarly, one or more of the components of controlled delivery drivemechanism 90100 and drug delivery device 10 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9010 is shown as two separate components upper housing9012A and lower housing 9012B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The novel controlleddelivery drive mechanisms of the present disclosure may be directly orindirectly activated by the user. Furthermore, the novel configurationsof the controlled delivery drive mechanism and drug delivery devices ofthe present disclosure maintain the sterility of the fluid pathwayduring storage, transportation, and through operation of the device.Because the path that the drug fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe drug container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent disclosure do not require terminal sterilization upon completionof assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connector, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a user, wherein aregulating mechanism acting to restrain the distribution of a tether isutilized to meter the free axial translation of the piston. The methodof operation of the drive mechanism and the drug delivery device may bebetter appreciated with reference to FIGS. 70A-70D and FIGS. 71A-71D, asdescribed above.

XVII. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 80A-85C, 86A-91, 92-99, and 100A-109B may be configuredto incorporate the embodiments of the drive mechanism described below inconnection with FIGS. 69A-73D. The embodiments of the drive mechanismdescribed below in connection with FIGS. 69A-73D may be used to replace,in its entirety or partially, the above-described drive mechanism 100,6100, 8100, 9210, 9310, 9410, or 9510, or any other drive mechanismdescribed herein, where appropriate.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances, controlled drug delivery pumpswith such drive mechanisms, the methods of operating such devices, andthe methods of assembling such devices. Notably, the multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The novel embodiments of the present disclosurethus are capable of delivering drug substances at variable rates. Thedrive mechanisms of the present disclosure may be pre-configurable ordynamically configurable, such as by control by the power and controlsystem, to meet desired delivery rates or profiles, as explained indetail below. Additionally, the drive mechanisms of the presentdisclosure provide integrated status indication features which providefeedback to the user before, during, and after drug delivery. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. Because theend-of-dose indication is related to the physical end of axialtranslation and/or travel of one or more components of the drivemechanism, the drive mechanism and drug delivery device provide a trueend-of-dose indication to the user. Through these mechanisms,confirmation of drug dose delivery can accurately be provided to theuser or administrator. Accordingly, the novel devices of the presentdisclosure alleviate one or more of the problems associated with priorart devices, such as those referred to above.

In a first embodiment, the present disclosure provides a multi-functiondrive mechanism which includes an actuator, a gear assembly including amain gear, a drive housing, and a drug container having a cap, apierceable seal (not visible), a barrel, and a plunger seal. The maingear may be, for example, a star gear disposed to contact multiplesecondary gears or gear surfaces. A drug chamber, located within thebarrel between the pierceable seal and the plunger seal, may contain adrug fluid for delivery through the insertion mechanism and drugdelivery device into the body of the user. A piston, and one or morebiasing members, wherein the one or more biasing members are initiallyretained in an energized state and is configured to bear upon aninterface surface of the piston, may also be incorporated in themulti-function drive mechanism. The piston is configured to translatesubstantially axially within a drug container having a plunger seal anda barrel. A tether is connected at one end to the piston and at anotherend to a winch drum/gear of a regulating mechanism, wherein the tetherrestrains the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The drug container may contain a drugfluid within a drug chamber for delivery to a user. Optionally, a coversleeve may be utilized between the biasing member and the interfacesurface of the piston to hide the interior components of the barrel(namely, the piston and the biasing member) from view during operationof the drive mechanism. The tether is configured to be released from awinch drum/gear of a regulating mechanism of the multi-function drivemechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

In at least one embodiment of the present disclosure, the regulatingmechanism is gear assembly driven by an actuator of the multi-functiondrive mechanism. The regulating mechanism retards or restrains thedistribution of tether, only allowing it to advance at a regulated ordesired rate. This restricts movement of piston within barrel, which ispushed by one or more biasing members, hence controlling the movement ofplunger seal and delivery of the drug contained in chamber. As theplunger seal advances in the drug container, the drug substance isdispensed through the sterile pathway connection, conduit, insertionmechanism, and into the body of the user for drug delivery. The actuatormay be a number of power/motion sources including, for example, a motor(e.g., a DC motor, AC motor, or stepper motor) or a solenoid (e.g.,linear solenoid, rotary solenoid). In a particular embodiment, theactuator is a rotational stepper motor with a notch that correspondswith the gear teeth of the main/star gear.

The regulating mechanism may further include one or more gears of a gearassembly. One or more of the gears may be, for example, compound gearshaving a small diameter gear attached at a shared center point to alarge diameter gear. The gear assembly may include a winch gear coupledto a winch drum/gear upon which the tether may be releasably wound.Accordingly, rotation of the gear assembly initiated by the actuator maybe coupled to winch drum/gear (i.e., through the gear assembly), therebycontrolling the distribution of tether, the rate of expansion of thebiasing members and the axial translation of the piston, and the rate ofmovement of plunger seal within barrel to force a fluid from drugchamber. The rotational movement of the winch drum/gear, and thus theaxial translation of the piston and plunger seal, are metered,restrained, or otherwise prevented from free axial translation by othercomponents of the regulating element, as described herein. Notably, theregulating mechanisms of the present disclosure do not drive thedelivery of fluid substances from the drug chamber. The delivery offluid substances from the drug chamber is caused by the expansion of thebiasing member from its initial energized state acting upon the pistonand plunger seal. The regulating mechanisms instead function to provideresistance to the free motion of the piston and plunger seal as they arepushed by the expansion of the biasing member from its initial energizedstate. The regulating mechanism does not drive the delivery but onlycontrols the delivery motion. The tether limits or otherwise restrainsthe motion of the piston and plunger seal, but does not apply the forcefor the delivery.

In addition to controlling the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer (thereby delivering drug substances at variable rates and/ordelivery profiles); the multi-function drive mechanisms of the presentdisclosure may concurrently or sequentially perform the steps of:triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a user; and connecting a sterile fluid pathway to adrug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. In at least oneembodiment, initial motion by the actuator of the multi-function drivemechanism causes rotation of main/star gear. In one manner, main/stargear conveys motion to the regulating mechanism through gear assembly.In another manner, main/star gear conveys motion to the needle insertionmechanism through gear. As gear is rotated by main/star gear, gearengages the needle insertion mechanism to initiate the fluid pathwayconnector into the user, as described in detail above. In one particularembodiment, needle insertion mechanism is a rotational needle insertionmechanism. Accordingly, gear is configured to engage a correspondinggear surface of the needle insertion mechanism. Rotation of gear causesrotation of needle insertion mechanism through the gear interactionbetween gear of the drive mechanism and corresponding gear surface ofthe needle insertion mechanism. Once suitable rotation of the needleinsertion mechanism occurs, the needle insertion mechanism may beinitiated to create the fluid pathway connector into the user, asdescribed in detail herein.

In at least one embodiment, rotation of the needle insertion mechanismin this manner may also cause a connection of a sterile fluid pathway toa drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the user. Ramp aspect ofneedle insertion mechanism is caused to bear upon a movable connectionhub of the sterile fluid pathway connector. As the needle insertionmechanism is rotated by the multi-function drive mechanism, ramp aspectof needle insertion mechanism bears upon and translates movableconnection hub of the sterile fluid pathway connector to facilitate afluid connection therein. In at least one embodiment, the needleinsertion mechanism may be configured such that a particular degree ofrotation enables the needle/trocar to retract as detailed above.Additionally or alternatively, such needle/trocar retraction may beconfigured to occur upon a user-activity or upon movement or function ofanother component of the drug delivery device. In at least oneembodiment, needle/trocar retraction may be configured to occur uponend-of-drug-delivery, as triggered by, for example, the regulatingmechanism and/or one or more of the status readers as described herein.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug delivery pump having ahousing and an assembly platform, upon which an activation mechanism, aninsertion mechanism, a fluid pathway connector, a power and controlsystem, and a controlled delivery drive mechanism may be mounted, saiddrive mechanism having a drive housing, a piston, and a biasing member,wherein the biasing member is initially retained in an energized stateand is configured to bear upon an interface surface of the piston. Thepiston is configured to translate substantially axially within a drugcontainer having a plunger seal and a barrel. A tether is connected atone end to the piston and at another end to a winch drum/gear of adelivery regulating mechanism, wherein the tether restrains the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The drug container may contain a drug fluid within a drug chamberfor delivery to a user. Optionally, a cover sleeve may be utilizedbetween the biasing member and the interface surface of the piston tohide the interior components of the barrel (namely, the piston and thebiasing member) from view during operation of the drive mechanism. Thetether is configured to be released from a winch drum/gear of thedelivery regulating mechanism to meter the free expansion of the biasingmember from its initial energized state and the free axial translationof the piston upon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch drum/gear upon which the tether may be releasably wound, rotationof the winch drum/gear releases the tether from the winch drum/gear tometer the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The metering of the tether controls therate or profile of drug delivery to a user. The piston may be one ormore parts and connects to a distal end of the tether. The winchdrum/gear is coupled to a regulating mechanism which controls rotationof the winch drum/gear and hence metering of the translation of thepiston.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch drum/gear and thereby permit axialtranslation of the piston by the biasing member to translate a plungerseal within a barrel. The one or more inputs may be provided by theactuation of the activation mechanism, a control interface, and/or aremote control mechanism. The power and control system may be configuredto receive one or more inputs to adjust the restraint provided by thetether and winch drum/gear on the free axial translation of the pistonupon which the biasing member bears upon to meet a desired drug deliveryrate or profile, to change the dose volume for delivery to the user,and/or to otherwise start, stop, or pause operation of the drivemechanism.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of the actuator. The change in the rate of movement ofthe actuator causes a change in the rotation rate of the regulatingmechanism which, in turn, controls the rate of drug delivery to theuser. Alternatively, the delivery profile may be altered by a change inthe characteristics of the flow path of medicament through the conduitconnecting the drug container and insertion mechanism. The change may becaused by the introduction, removal, or modification of a flowrestrictor which restricts flow of medicament from the drug container tothe insertion mechanism. For example, a flow restrictor may havemultiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

The present disclosure provides multi-function drive mechanisms for thecontrolled delivery of drug substances and drug delivery pumps whichincorporate such multi-function drive mechanisms. The multi-functiondrive mechanisms of the present disclosure enable or initiate severalfunctions, including: (i) controlling the rate of drug delivery bymetering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. The drive mechanisms of the present disclosurecontrol the rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container and, thus, are capableof delivering drug substances at variable rates and/or deliveryprofiles. Additionally, the drive mechanisms of the present disclosureprovide integrated status indication features which provide feedback tothe user before, during, and after drug delivery. For example, the usermay be provided an initial feedback to identify that the system isoperational and ready for drug delivery. Upon activation, the system maythen provide one or more drug delivery status indications to the user.At completion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication.

The novel devices of the present disclosure provide drive mechanismswith integrated status indication and drug delivery pumps whichincorporate such drive mechanisms. Such devices are safe and easy touse, and are aesthetically and ergonomically appealing forself-administering patients. The devices described herein incorporatefeatures which make activation, operation, and lock-out of the devicesimple for even untrained users. The novel devices of the presentdisclosure provide these desirable features without any of the problemsassociated with known prior art devices. Certain non-limitingembodiments of the novel drug delivery pumps, drive mechanisms, andtheir respective components are described further herein with referenceto the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.69A-69C show an exemplary drug delivery device according to at least oneembodiment of the present disclosure with the top housing removed sothat the internal components are visible. The drug delivery device maybe utilized to administer delivery of a drug treatment into a body of auser. As shown in FIGS. 69A-69C, the drug delivery device 9010 includesa pump housing 9012. Pump housing 9012 may include one or more housingsubcomponents which are fixedly engageable to facilitate easiermanufacturing, assembly, and operation of the drug delivery device. Forexample, drug delivery device 9010 includes a pump housing 9012 whichmay include an upper housing and a lower housing (not shown for ease ofviewing internal components). The drug delivery device may furtherinclude an activation mechanism, a status indicator, and a window.Window may be any translucent or transmissive surface through which theoperation of the drug delivery device may be viewed. As shown in FIG.69B, drug delivery device 9010 further includes assembly platform 9020,sterile fluid conduit 9030, drive mechanism 90100 having drug container9050, insertion mechanism 90200, fluid pathway connector 90300, and apower and control system (not shown). One or more of the components ofsuch drug delivery devices may be modular in that they may be, forexample, pre-assembled as separate components and configured intoposition onto the assembly platform 9020 of the drug delivery device9010 during manufacturing.

The pump housing 9012 contains all of the device components and providesa means of removably attaching the device 9010 to the skin of the user.The pump housing 9012 also provides protection to the interiorcomponents of the device 9010 against environmental influences. The pumphousing 9012 is ergonomically and aesthetically designed in size, shape,and related features to facilitate easy packaging, storage, handling,and use by users who may be untrained and/or physically impaired.Furthermore, the external surface of the pump housing 9012 may beutilized to provide product labeling, safety instructions, and the like.Additionally, as described above, housing 9012 may include certaincomponents, such as one or more status indicators and windows, which mayprovide operation feedback to the user.

In at least one embodiment, the drug delivery device 9010 provides anactivation mechanism that is displaced by the user to trigger the startcommand to the power and control system. In a preferred embodiment, theactivation mechanism is a start button that is located through the pumphousing 9012, such as through an aperture between upper housing andlower housing, and which contacts either directly or indirectly thepower and control system. In at least one embodiment, the start buttonmay be a push button, and in other embodiments, may be an on/off switch,a toggle, or any similar activation feature known in the art. The pumphousing 9012 also provides one or more status indicators and windows. Inother embodiments, one or more of the activation mechanism, the statusindicator, the window, and combinations thereof may be provided on theupper housing or the lower housing such as, for example, on a sidevisible to the user when the drug delivery device 9010 is placed on thebody of the user. Housing 9012 is described in further detailhereinafter with reference to other components and embodiments of thepresent disclosure.

Drug delivery device 9010 is configured such that, upon activation by auser by depression of the activation mechanism, the multi-function drivemechanism is activated to: insert a fluid pathway into the user; enable,connect, or open necessary connections between a drug container, a fluidpathway, and a sterile fluid conduit; and force drug fluid stored in thedrug container through the fluid pathway and fluid conduit for deliveryinto a user. In at least one embodiment, such delivery of drug fluidinto a user is performed by the multi-function drive mechanism in acontrolled manner. One or more optional safety mechanisms may beutilized, for example, to prevent premature activation of the drugdelivery device. For example, an optional on-body sensor (not visible)may be provided in one embodiment as a safety feature to ensure that thepower and control system, or the activation mechanism, cannot be engagedunless the drug delivery device 9010 is in contact with the body of theuser. In one such embodiment, the on-body sensor is located on thebottom of lower housing where it may come in contact with the user'sbody. Upon displacement of the on-body sensor, depression of theactivation mechanism is permitted. Accordingly, in at least oneembodiment the on-body sensor is a mechanical safety mechanism, such asfor example a mechanical lock out, that prevents triggering of the drugdelivery device 9010 by the activation mechanism. In another embodiment,the on-body sensor may be an electro-mechanical sensor such as amechanical lock out that sends a signal to the power and control systemto permit activation. In still other embodiments, the on-body sensor canbe electrically based such as, for example, a capacitive- orimpedance-based sensor which must detect tissue before permittingactivation of the power and control system. These concepts are notmutually exclusive and one or more combinations may be utilized withinthe breadth of the present disclosure to prevent, for example, prematureactivation of the drug delivery device. In a preferred embodiment, thedrug delivery device 9010 utilizes one or more mechanical on-bodysensors. Additional integrated safety mechanisms are described hereinwith reference to other components of the novel drug delivery devices.

XVII.A. Power and Control System:

The power and control system may include a power source, which providesthe energy for various electrical components within the drug deliverydevice, one or more feedback mechanisms, a microcontroller, a circuitboard, one or more conductive pads, and one or more interconnects. Othercomponents commonly used in such electrical systems may also beincluded, as would be appreciated by one having ordinary skill in theart. The one or more feedback mechanisms may include, for example,audible alarms such as piezo alarms and/or light indicators such aslight emitting diodes (LEDs). The microcontroller may be, for example, amicroprocessor. The power and control system controls several deviceinteractions with the user and interfaces with the drive mechanism90100. In one embodiment, the power and control system interfaces eitherdirectly or indirectly with the on-body sensor 9024 to identify when thedevice is in contact with the user and/or the activation mechanism toidentify when the device has been activated. The power and controlsystem may also interface with the status indicator of the pump housing9012, which may be a transmissive or translucent material which permitslight transfer, to provide visual feedback to the user. The power andcontrol system interfaces with the drive mechanism 90100 through one ormore interconnects to relay status indication, such as activation, drugdelivery, and end-of-dose, to the user. Such status indication may bepresented to the user via auditory tones, such as through the audiblealarms, and/or via visual indicators, such as through the LEDs. In apreferred embodiment, the control interfaces between the power andcontrol system and the other components of the drug delivery device arenot engaged or connected until activation by the user. This is adesirable safety feature that prevents accidental operation of the drugdelivery device and may additionally maintain the energy contained inthe power source during storage, transportation, and the like.

The power and control system may be configured to provide a number ofdifferent status indicators to the user. For example, the power andcontrol system may be configured such that after the on-body sensorand/or trigger mechanism have been pressed, the power and control systemprovides a ready-to-start status signal via the status indicator ifdevice start-up checks provide no errors. After providing theready-to-start status signal and, in an embodiment with the optionalon-body sensor, if the on-body sensor remains in contact with the bodyof the user, the power and control system will power the drive mechanism90100 to begin delivery of the drug treatment through the fluid pathwayconnector 90300 and sterile fluid conduit 9030 (not shown).

Additionally, the power and control system may be configured to identifyremoval of the drug delivery device from its packaging. The power andcontrol system may be mechanically, electronically, orelectro-mechanically connected to the packaging such that removal of thedrug delivery device from the packaging may activate or power-on thepower and control system for use, or simply enable the power and controlsystem to be powered-on by the user. In such an embodiment, withoutremoval of the drug delivery device from the packaging the drug deliverydevice cannot be activated. This provides an additional safety mechanismof the drug delivery device and for the user. In at least oneembodiment, the drug delivery device or the power and control system maybe electronically or electro-mechanically connected to the packaging,for example, such as by one or more interacting sensors from a range of:Hall effect sensors; giant magneto resistance (GMR) or magnetic fieldsensors; optical sensors; capacitive or capacitance change sensors;ultrasonic sensors; and linear travel, LVDT, linear resistive, orradiometric linear resistive sensors; and combinations thereof, whichare capable of coordinating to transmit a signal between components toidentify the location there-between. Additionally or alternatively, thedrug delivery device or the power and control system may be mechanicallyconnected to the packaging, such as by a pin and slot relationship whichactivates the system when the pin is removed (i.e., once the drugdelivery device is removed from the packaging).

In a preferred embodiment of the present disclosure, once the power andcontrol system has been activated, the multi-function drive mechanism isinitiated to actuate the insertion mechanism 90200 and the fluid pathwayconnector 90300, while also permitting the drug fluid to be forced fromthe drug container. During the drug delivery process, the power andcontrol system is configured to provide a dispensing status signal viathe status indicator. After the drug has been administered into the bodyof the user and after the end of any additional dwell time, to ensurethat substantially the entire dose has been delivered to the user, thepower and control system may provide an okay-to-remove status signal viathe status indicator. This may be independently verified by the user byviewing the drive mechanism and drug dose delivery through the window ofthe pump housing 9012. Additionally, the power and control system may beconfigured to provide one or more alert signals via the statusindicator, such as for example alerts indicative of fault or operationfailure situations.

The power and control system may additionally be configured to acceptvarious inputs from the user to dynamically control the drive mechanisms90100 to meet a desired drug delivery rate or profile. For example, thepower and control system may receive inputs, such as from partial orfull activation, depression, and/or release of the activation mechanism,to set, initiate, stop, or otherwise adjust the control of the drivemechanism 90100 via the power and control system to meet the desireddrug delivery rate or profile. Similarly, the power and control systemmay be configured to receive such inputs to adjust the drug dose volume;to prime the drive mechanism, fluid pathway connector, and fluidconduit; and/or to start, stop, or pause operation of the drivemechanism 90100. Such inputs may be received by the user directly actingon the drug delivery device 9010, such as by use of the activationmechanism 9014 or a different control interface, or the power andcontrol system may be configured to receive such inputs from a remotecontrol device. Additionally or alternatively, such inputs may bepre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism of the drugdelivery device 9010 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

XVII.B. Insertion Mechanism

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or user, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure, including a rigid needle insertion mechanismand/or a rotational needle insertion mechanism as developed by theassignee of the present disclosure.

In at least one embodiment, the insertion mechanism 90200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 69B and FIG. 69C). The connection of the base to theassembly platform 9020 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the user. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 9010. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 9030 topermit fluid flow through the manifold, cannula, and into the body ofthe user during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a9027 gauge solid core trocar and in other embodiments, the needle may beany size needle suitable to insert the cannula for the type of drug anddrug administration (e.g., subcutaneous, intramuscular, intradermal,etc.) intended. A sterile boot may be utilized within the needleinsertion mechanism. The sterile boot is a collapsible sterile membranethat is in fixed engagement at a proximal end with the manifold and at adistal end with the base. In at least on embodiment, the sterile boot ismaintained in fixed engagement at a distal end between base andinsertion mechanism housing. Base includes a base opening through whichthe needle and cannula may pass-through during operation of theinsertion mechanism, as will be described further below. Sterility ofthe cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle and cannula are maintained in the sterileenvironment of the manifold and sterile boot. The base opening of basemay be closed from non-sterile environments as well, such as by forexample a sealing membrane (not visible).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. Displacement of the lockoutpin(s), by one or more methods such as pulling, pushing, sliding, and/orrotation, permits insertion biasing member to decompress from itsinitial compressed, energized state. This decompression of the insertionbiasing member drives the needle and, optionally, the cannula into thebody of the user. At the end of the insertion stage or at the end ofdrug delivery (as triggered by the multi-function drive mechanism), theretraction biasing member is permitted to expand in the proximaldirection from its initial energized state. This axial expansion in theproximal direction of the retraction biasing member retracts the needle.If an inserter needle/trocar and cannula configuration are utilized,retraction of the needle may occur while maintaining the cannula influid communication with the body of the user. Accordingly, theinsertion mechanism may be used to insert a needle and cannula into theuser and, subsequently, retract the needle while retaining the cannulain position for drug delivery to the body of the user.

XVII.C. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9010, the fluid pathway connector 90300 isenabled to connect the sterile fluid conduit 9030 to the drug containerof the drive mechanism 90100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 90100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the body ofthe user. In one such embodiment, the fluid pathway connector may besubstantially similar to that described in International PatentApplication No. PCT/US2012/054861, which is included by reference hereinin its entirety for all purposes. In such an embodiment, a compressiblesterile sleeve may be fixedly attached between the cap of the drugcontainer and the connection hub of the fluid pathway connector. Thepiercing member may reside within the sterile sleeve until a connectionbetween the fluid connection pathway and the drug container is desired.The sterile sleeve may be sterilized to ensure the sterility of thepiercing member and the fluid pathway prior to activation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Applications No.PCT/US2013/030478 or No. PCT/US2014/052329, for example, which areincluded by reference herein in their entirety for all purposes.According to such an embodiment, a drug container may have a drugchamber within a barrel between a pierceable seal and a plunger seal. Adrug fluid is contained in the drug chamber. Upon activation of thedevice by the user, a drive mechanism asserts a force on a plunger sealcontained in the drug container. As the plunger seal asserts a force onthe drug fluid and any air/gas gap or bubble, a combination of pneumaticand hydraulic pressure builds by compression of the air/gas and drugfluid and the force is relayed to the sliding pierceable seal. Thepierceable seal is caused to slide towards the cap, causing it to bepierced by the piercing member retained within the integrated sterilefluid pathway connector. Accordingly, the integrated sterile fluidpathway connector is connected (i.e., the fluid pathway is opened) bythe combination pneumatic/hydraulic force of the air/gas and drug fluidwithin the drug chamber created by activation of a drive mechanism. Oncethe integrated sterile fluid pathway connector is connected or opened,drug fluid is permitted to flow from the drug container, through theintegrated sterile fluid pathway connector, sterile fluid conduit, andinsertion mechanism, and into the body of the user for drug delivery. Inat least one embodiment, the fluid flows through only a manifold and acannula and/or needle of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery.

In a preferred embodiment, the sterile fluid pathway connector isinitiated by movement of the needle insertion mechanism, which itself isinitiated by the multi-function drive mechanism. Additionally oralternatively, the sterile fluid pathway connector is initiated bymovement directly of the multi-function drive mechanism. For example,the multi-function drive mechanism may include a rotational gear, suchas the star gear described in detail herein, that acts concurrently orsequentially to control the rate of drug delivery, to actuate the needleinsertion mechanism, and/or initiate the sterile fluid pathwayconnector. In one particular embodiment, shown in FIGS. 69A-69C, themulti-function drive mechanism performs all of these steps substantiallyconcurrently. The multi-function drive mechanism rotates a gear thatacts upon several other components. The gear acts on a gear assembly tocontrol the rate of drug delivery, while also contacting a needleinsertion mechanism to introduce a fluid pathway into the user. As theneedle insertion mechanism is initiated, the sterile fluid connection ismade to permit drug fluid flow from the drug container, through thefluid conduit, into the needle insertion mechanism, for delivery intothe patient as the gear and gear assembly of the multi-function drivemechanism control the rate of drug delivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 90300 and the sterile fluid conduit 30 are providedhereinafter in later sections in reference to other embodiments.

XVII.D. Multi-Function Drive Mechanism

The multi-function drive mechanisms of the present disclosure enable orinitiate several functions, including: (i) controlling the rate of drugdelivery by metering, providing resistance, or otherwise preventing freeaxial translation of the plunger seal utilized to force a drug substanceout of a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a user; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the user. With reference to the embodiments shown in FIGS.70A-70D and 3A-3D, multi-function drive mechanism 90100 includes anactuator 90101, a gear assembly 90110 including a main gear 90102, adrive housing 90130, and a drug container 9050 having a cap 9052, apierceable seal (not visible), a barrel 9058, and a plunger seal 9060.The main gear 90102 may be, for example, a star gear disposed to contactmultiple secondary gears or gear surfaces. A drug chamber 9021, locatedwithin the barrel 9058 between the pierceable seal and the plunger seal9060, may contain a drug fluid for delivery through the insertionmechanism and drug delivery device into the body of the user. The sealsdescribed herein may be comprised of a number of materials but are, in apreferred embodiment, comprised of one or more elastomers or rubbers.The drive mechanism 90100 may further contain one or more drive biasingmembers, one or more release mechanisms, and one or more guides, as aredescribed further herein. The components of the drive mechanism functionto force a fluid from the drug container out through the pierceableseal, or preferably through the piercing member of the fluid pathwayconnector, for delivery through the fluid pathway connector, sterilefluid conduit, and insertion mechanism into the body of the user.

In one particular embodiment, the drive mechanism 90100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. The fluid pathway connector may beconnected through the pierceable seal prior to, concurrently with, orafter activation of the drive mechanism to permit fluid flow from thedrug container, through the fluid pathway connector, sterile fluidconduit, and insertion mechanism, and into the body of the user for drugdelivery. In at least one embodiment, the fluid flows through only amanifold and a cannula of the insertion mechanism, thereby maintainingthe sterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detail herein.

Referring now to the embodiment of the multi-function drive mechanismshown in FIGS. 70A-70D and 71A-71D, multi-function drive mechanism 90100includes an actuator 90101, a gear assembly 110 including a main gear90102, a drive housing 90130, and a drug container 9050 having a cap9052, a pierceable seal (not visible), a barrel 9058, and a plunger seal9060. The main gear 90102 may be, for example, a star gear disposed tocontact multiple secondary gears or gear surfaces. A drug chamber 9021,located within the barrel 9058 between the pierceable seal and theplunger seal 9060, may contain a drug fluid for delivery through theinsertion mechanism and drug delivery device into the body of the user.Compressed within the drive housing 90130, between the drug container9050 and the proximal end of the housing 90130, are one or more drivebiasing members 90122 and a piston 90110, wherein the drive biasingmembers 90122 are configured to bear upon an interface surface 90110C ofthe piston 90110, as described further herein. Optionally, a coversleeve (not shown) may be utilized between the drive biasing members90122 and the interface surface 90110C of the piston 90110 to, forexample, promote more even distribution of force from the drive biasingmember 90122 to the piston 90110, prevent buckling of the drive biasingmembers 90122, and/or hide biasing members 90122 from user view.Interface surface 90110C of piston 90110 is caused to rest substantiallyadjacent to, or in contact with, a proximal end of seal 9060. Althoughthe embodiments shown in FIGS. 70A-70D and 71A-71D show a singularbiasing member it is also contemplated that one or more biasing membersdisposed to act in parallel may be used.

As best shown in FIG. 70D and FIG. 71D, the piston 90110 may becomprised of two components 90110A and 90110B and have an interfacesurface 90110C to contact the plunger seal. A tether, ribbon, string, orother retention strap (referred to herein as the “tether” 90525) may beconnected at one end to the piston 90110A, 90110B. For example, thetether 90525 may be connected to the piston 90110A, 90110B by retentionbetween the two components of the piston 90110A, 90110B when assembled.The tether 90525 is connected at another end to a winch drum/gear 90520of a delivery control mechanism 90500. Through the use of the winchdrum/gear 90520 connected to one end of the tether 90525, and the tether90525 connected at another end to the piston 90110A, 90110B, theregulating mechanism 90500 functions to control, meter, provideresistance, or otherwise prevent free axial translation of the piston90110A, 90110B and plunger seal 9060 utilized to force a drug substanceout of a drug container 9050. Accordingly, the regulating mechanism90500 is a portion of the gear assembly 90116 aspect of themulti-function drive mechanism, which together function to control therate or profile of drug delivery to the user.

As shown in FIGS. 70A-70D and 71A-71D, and in isolation in FIGS. 72 and73A-73B, in the embodiments of the present disclosure, the regulatingmechanism 90500 is gear assembly driven by an actuator 90101 of themulti-function drive mechanism 90100. The regulating mechanism retardsor restrains the distribution of tether 90525, only allowing it toadvance at a regulated or desired rate. This restricts movement ofpiston 90110 within barrel 9058, which is pushed by one or more biasingmembers 90122, hence controlling the movement of plunger seal 9060 anddelivery of the drug contained in chamber 9021. As the plunger seal 9060advances in the drug container 9050, the drug substance is dispensedthrough the sterile pathway connection 90300, conduit 9030, insertionmechanism 90200, and into the body of the user for drug delivery. Theactuator 90101 may be a number of power/motion sources including, forexample, a solenoid, a stepper motor, or a rotational drive motor. In aparticular embodiment, the actuator 90101 is a rotational stepper motorwith a notch that corresponds with the gear teeth of the main/star gear90102. Commonly, such a rotational stepper motor may be referred to as a‘Pac-Man’ motor. In at least one embodiment, the Pac-Man motor has agear interface within which one or more teeth of the main gear maypartially reside during operation of the system. This is more clearlyvisible in FIGS. 73A-73B. When the gear interface 90101A of the Pac-Manmotor 90101 is in alignment with a tooth 90102A of the main gear 90102,rotational motion of the Pac-Man motor 90101 causes gear interfacerotation of the main gear 90102. When the Pac-Man motor 90101 is betweengear teeth of the main gear, it may act as a resistance for, forexample, back-spinning or unwinding of the gear assembly 90116. Furtherdetail about the gear assembly 90116, regulating mechanism 90500, andmulti-function drive mechanism 90100 are provided herein.

In a particular embodiment shown in FIGS. 73A-73B, the regulatingelement 90500 further includes one or more gears 90511, 90512, 90513,90514, of a gear assembly 90516. One or more of the gears 90511, 90512,90513, 90514 may be, for example, compound gears having a small diametergear attached at a shared center point to a large diameter gear. Gear90513 may be rotationally coupled to winch drum/gear 90520, for exampleby a keyed shaft, thereby coupling rotation of gear assembly 90516 towinch drum/gear 90520. Compound gear 90512 engages the small diametergear 90513 such that rotational movement of the compound gear aspect90512B is conveyed by engagement of the gears (such as by engagement ofcorresponding gear teeth) to gear 90513. Compound gear aspect 90512A,the rotation of which is coupled to gear aspect 90512B, is caused torotate by action of compound gear aspect 90102B of the main/star gear90102. Compound gear aspect 90102B, the rotation of which is coupled tomain/star gear 90102, is caused to rotate by interaction betweenmain/star gear 90102A and interface 90101A of the actuator 90101. Thus,rotation of main/star gear 90102 is conveyed to winch drum/gear 90520.Accordingly, rotation of the gear assembly 90516 initiated by theactuator 90101 may be coupled to winch drum/gear 90520 (i.e., throughthe gear assembly 90516), thereby controlling the distribution of tether90525, and the rate of movement of plunger seal 9060 within barrel 9058to force a fluid from drug chamber 9021. The rotational movement of thewinch drum/gear 90520, and thus the axial translation of the piston90110 and plunger seal 9060, are metered, restrained, or otherwiseprevented from free axial translation by other components of theregulating element 90500, as described herein. As described above, theactuator 90101 may be a number of known power/motion sources including,for example, a motor (e.g., a DC motor, AC motor, or stepper motor) or asolenoid (e.g., linear solenoid, rotary solenoid).

Notably, the regulating mechanisms 90500 of the present disclosure donot drive the delivery of fluid substances from the drug chamber 9021.The delivery of fluid substances from the drug chamber 9021 is caused bythe expansion of the biasing member 90122 from its initial energizedstate acting upon the piston 90110A, 90110B and plunger seal 9060. Theregulating mechanisms 90500 instead function to provide resistance tothe free motion of the piston 90110A, 90110B and plunger seal 9060 asthey are pushed by the expansion of the biasing member 90122 from itsinitial energized state. The regulating mechanism 90500 does not drivethe delivery but only controls the delivery motion. The tether limits orotherwise restrains the motion of the piston 90110 and plunger seal9060, but does not apply the force for the delivery. According to apreferred embodiment, the controlled delivery drive mechanisms and drugdelivery devices of the present disclosure include a regulatingmechanism indirectly or directly connected to a tether metering theaxial translation of the piston 90110A, 90110B and plunger seal 9060,which are being driven to axially translate by the biasing member 90122.The rate of drug delivery as controlled by the regulating mechanism maybe determined by: selection of the gear ratio of gear assembly 90516;selection of the main/star gear 90102; selection of the diameter ofwinding drum/gear 90520; using electromechanical actuator 90101 tocontrol the rate of rotation of the main/star gear 90102; or any othermethod known to one skilled in the art. By using electromechanicalactuator 90101 the rate of rotation of the main/star gear 90102 it maybe possible to configure a drug delivery device to provide a variabledose rate (i.e., the rate of drug delivery is varied during atreatment).

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether 90525 by the winch drum/gear 90520 and thereby permitaxial translation of the piston 90110 by the biasing member 90122 totranslate a plunger seal 9060 within a barrel 9058. The one or moreinputs may be provided by the actuation of the activation mechanism, acontrol interface, and/or a remote control mechanism. The power andcontrol system may be configured to receive one or more inputs to adjustthe restraint provided by the tether 90525 and winch drum/gear 90520 onthe free axial translation of the piston 90110 upon which the biasingmember 90122 bears upon to meet a desired drug delivery rate or profile,to change the dose volume for delivery to the user, and/or to otherwisestart, stop, or pause operation of the drive mechanism.

The components of the drive mechanism 90100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9060 of the drug container 9050. Optionally, the drive mechanism90100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9060 to, for example,ensure that substantially the entire drug dose has been delivered to theuser. For example, the plunger seal 9060, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user.

The tether 90525 may have one or more status triggers, such aselectrical contacts, optical markings, or electromechanical pins orrecesses, which are capable of contacting or being recognized by astatus reader. In at least one embodiment, an end-of-dose statusindication may be provided to the user once the status reader contactsor recognizes the final status trigger positioned on the tether 90525that would contact the status reader at the end of axial travel of thepiston 90110A, 90110B and plunger 9060 within the barrel 9058 of thedrug container 9050. The status reader may be, for example, anelectrical switch reader to contact the corresponding electricalcontacts, an optical reader to recognize the corresponding opticalmarkings, or a mechanical or electromechanical reader configured tocontact corresponding pins, holes, or similar aspects on the tether. Thestatus triggers may be positioned along the tether 90525 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asthe drug delivery device is activated and drug delivery is begun byrelease of the biasing member 90122 and the resulting force applied tothe piston 90110A, 90110B and plunger seal 9060, the rate or profile ofdrug delivery to the user is controlled by the regulating mechanism90500, gear assembly 90516, and winch drum/gear 90520 releasing thetether 90525 and permitting expansion of the biasing member 90122 andaxial translation of the piston 90110A, 90110B and plunger seal 9060. Asthis occurs, the status triggers of the tether 90525 are contacted orrecognized by the status reader and the status of the drive mechanismbefore, during, and after operation can be relayed to the power andcontrol system to provide feedback to the user. Depending on the numberof status triggers located on the tether 90525, the frequency of theincremental status indication may be varied as desired. As describedabove, a range of status readers may be utilized depending on the statustriggers utilized by the system.

In a preferred embodiment, the status reader may apply a tensioningforce to the tether 90525. When the system reaches end-of-dose, thetether 90525 goes slack and the status reader 90544 is permitted torotate about a fulcrum. This rotation may operate an electrical orelectromechanical switch, for example a switch, signaling slack in thetether 90525 to the power and control system. Additionally, a gear 90511of gear assembly 90516 may act as an encoder along with a sensor. Thesensor/encoder combination is used to provide feedback of gear assemblyrotation, which in turn can be calibrated to the position of piston90110 when there is no slack in the tether 90525. Together, the statusreader and sensor/encoder may provide positional feedback, end-of-dosesignal, and error indication, such as an occlusion, by observing slackin the tether 90525 prior to reaching the expected number of motorrotations as counted by the sensor/encoder.

Referring back to FIGS. 70A-70D and 71A-71D, in addition to controllingthe rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container (thereby deliveringdrug substances at variable rates and/or delivery profiles); themulti-function drive mechanisms of the present disclosure mayconcurrently or sequentially perform the steps of: triggering a needleinsertion mechanism to provide a fluid pathway for drug delivery to auser; and connecting a sterile fluid pathway to a drug container topermit fluid flow from the drug container to the needle insertionmechanism for delivery to the user. In at least one embodiment, as shownin FIGS. 70A-70D and 71A-71D, initial motion by the actuator 90101 ofthe multi-function drive mechanism 90100 causes rotation of main/stargear 90102. Main/star gear 90102 is shown as a compound gear withaspects 90102A and 90102B (see FIG. 72). In one manner, main/star gear90102 conveys motion to the regulating mechanism 90500 through gearassembly 90516. In another manner, main/star gear 90102 conveys motionto the needle insertion mechanism 90200 through gear 90112. As gear90112 is rotated by main/star gear 90102, gear 90112 engages the needleinsertion mechanism 90200 to initiate the fluid pathway connector intothe user, as described in detail above. In one particular embodiment,needle insertion mechanism 90200 is a rotational needle insertionmechanism. Accordingly, gear 90112 is configured to engage acorresponding gear surface 90208 of the needle insertion mechanism90200. Rotation of gear 90112 causes rotation of needle insertionmechanism 90200 through the gear interaction between gear 90112 of thedrive mechanism 90100 and corresponding gear surface 90208 of the needleinsertion mechanism 90200. Once suitable rotation of the needleinsertion mechanism 90200 occurs, for example rotation along axis ‘R’shown in FIG. 70B-70C, the needle insertion mechanism may be initiatedto create the fluid pathway connector into the user, as described indetail above.

As shown in FIGS. 70A-70D and 71A-71D, rotation of the needle insertionmechanism 90200 in this manner may also cause a connection of a sterilefluid pathway to a drug container to permit fluid flow from the drugcontainer to the needle insertion mechanism for delivery to the user.Ramp aspect 90222 of needle insertion mechanism 90200 is caused to bearupon a movable connection hub 90322 of the sterile fluid pathwayconnector 90300. As the needle insertion mechanism 90200 is rotated bythe multi-function drive mechanism 90100, ramp aspect 90222 of needleinsertion mechanism 90200 bears upon and translates movable connectionhub 90322 of the sterile fluid pathway connector 90300 to facilitate afluid connection therein. Such translation may occur, for example, inthe direction of the hollow arrow along axis ‘C’ shown in FIGS. 70B and71B. In at least one embodiment, the needle insertion mechanism 90200may be configured such that a particular degree of rotation uponrotational axis ‘R’ (shown in FIGS. 70B-70C) enables the needle/trocarto retract as detailed above. Additionally or alternatively, suchneedle/trocar retraction may be configured to occur upon a user-activityor upon movement or function of another component of the drug deliverydevice. In at least one embodiment, needle/trocar retraction may beconfigured to occur upon end-of-drug-delivery, as triggered by, forexample, the regulating mechanism 90500 and/or one or more of the statusreaders as described above. During these stages of operation, deliveryof fluid substances from the drug chamber 9021 may be initiated,on-going, and/or completed by the expansion of the biasing member 90122from its initial energized state acting upon the piston 90110A, 90110Band plunger seal 9060. As described above, the regulating mechanisms90500 function to provide resistance to the free motion of the piston90110A, 90110B and plunger seal 9060 as they are pushed by the expansionof the biasing member 90122 from its initial energized state. Theregulating mechanism 90500 does not drive the delivery but only controlsthe delivery motion. The tether limits or otherwise restrains the motionof the piston 90110 and plunger seal 9060, but does not apply the forcefor the delivery. This is visible through the progression of thecomponents shown in FIGS. 70A-70D and 71A-71D. The motion of the piston90110A, 90110B and plunger seal 9060 as they are pushed by the expansionof the biasing member 90122 from its initial energized state are shownin the direction of the solid arrow along axis ‘A’ from proximal orfirst position ‘P’ to the distal or second position ‘D’, as shown in thetransition of FIGS. 70A-70D and 71A-71D.

Further aspects of the novel drive mechanism will be described withreference to FIG. 72 and FIGS. 73A-73B. FIG. 72 shows a perspective viewof the multi-function drive mechanism, according to at least a firstembodiment, during its initial locked stage. Initially, the tether 90525may retain the biasing member 90122 in an initial energized positionwithin piston 90110A, 90110B. Directly or indirectly upon activation ofthe device by the user, the multi-function drive mechanism 90100 may beactivated to permit the biasing member to impart a force to piston 90110and therefore to tether 90525. This force on tether 90525 imparts atorque on winding drum 90520 which causes the gear assembly 90516 andregulating mechanism 90500 to begin motion. As shown in FIG. 73A, thepiston 90110 and biasing member 90122 are both initially in acompressed, energized state behind the plunger seal 9060. The biasingmember 90122 may be maintained in this state until activation of thedevice between internal features of drive housing 90130 and interfacesurface 90110C of piston 90110A, 90110B. As the drug delivery device 10is activated and the drive mechanism 90100 is triggered to operate,biasing member 90122 is permitted to expand (i.e., decompress) axiallyin the distal direction (i.e., in the direction of the solid arrow shownin FIGS. 70A-70D and FIGS. 71A-71D). Such expansion causes the biasingmember 90122 to act upon and distally translate interface surface 90110Cand piston 90110, thereby distally translating plunger seal 9060 to pushdrug fluid out of the drug chamber 9021 of barrel 9058. In at least oneembodiment, an end-of-dose status indication may be provided to the useronce the status reader contacts or recognizes a status triggerpositioned on the tether 90525 to substantially correspond with the endof axial travel of the piston 90110A, 90110B and plunger seal 9060within the barrel 9058 of the drug container 9050. The status triggersmay be positioned along the tether 90525 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the user. In at least one embodiment,the status reader is an optical status reader configured to recognizethe corresponding optical status triggers on the tether. As would beunderstood by an ordinarily skilled artisan, such optical statustriggers may be markings which are recognizable by the optical statusreader. In another embodiment, the status reader is a mechanical orelectromechanical reader configured to physically contact correspondingpins, holes, or similar aspects on the tether. Electrical contacts couldsimilarly be utilized on the tether as status indicators which contactor are otherwise recognized by the corresponding electrical statusreader. The status triggers may be positioned along the tether 90525 tobe read or recognized at positions which correspond with the beginningand end of drug delivery, as well as at desired increments during drugdelivery. As shown, tether 90525 passes substantially axially throughthe drive mechanism housing 90130, the biasing member 90122, andconnects to the piston 90110 A, 90110B to restrict the axial translationof the piston 90110A, 90110B and the plunger seal 9060 that residesadjacent thereto.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement ofwinding drum 90520 and, thus, axial translation of the components of thecontrolled delivery drive mechanism 90100. Accordingly, the regulatingmechanism 90500 only controls the motion of the drive mechanism, butdoes not apply the force for the drug delivery. One or more additionalbiasing members 90122, such as compression springs, may be utilized todrive or assist the driving of the piston 90110. For example, acompression spring may be utilized within the drive housing 90130 forthis purpose. The regulating mechanism 90500 only controls, meters, orregulates such action. The controlled delivery drive mechanisms and/ordrug delivery devices of the present disclosure may additionally enablea compliance push to ensure that substantially all of the drug substancehas been pushed out of the drug chamber 9021. The plunger seal 9060,itself, may have some compressibility permitting a compliance push ofdrug fluid from the drug container. For example, when a pop-out plungerseal is employed, i.e., a plunger seal that is deformable from aninitial state, the plunger seal may be caused to deform or “pop-out” toprovide a compliance push of drug fluid from the drug container.Additionally or alternatively, an electromechanical status switch andinterconnect assembly may be utilized to contact, connect, or otherwiseenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

In at least one embodiment, incremental status indication may beprovided to the user by reading or recognizing the rotational movementof one or more gears of gear assembly 90516. As the gear assembly 90516rotates, a status reader may read or recognize one or more correspondingstatus triggers on one of the gears in the gear assembly to provideincremental status indication before, during, and after operation of thevariable rate controlled delivery drive mechanism. A number of statusreaders may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism may utilize a mechanicalstatus reader which is physically contacted by gear teeth of one of thegears of the gear assembly. As the status reader is contacted by thestatus trigger(s), which in this exemplary embodiment may be the gearteeth of one of the gears (or holes, pins, ridges, markings, electricalcontacts, or the like, upon the gear), the status reader measures therotational position of the gear and transmits a signal to the power andcontrol system for status indication to the user. Additionally oralternatively, the drive mechanism may utilize an optical status reader.The optical status reader may be, for example, a light beam that iscapable of recognizing a motion and transmitting a signal to the powerand control system. For example, the drive mechanism may utilize anoptical status reader that is configured to recognize motion of the gearteeth of one of the gears in the gear assembly (or holes, pins, ridges,markings, electrical contacts, or the like, upon the gear). Similarly,the status reader may be an electrical switch configured to recognizeelectrical contacts on the gear. In any of these embodiments, the sensormay be utilized to then relay a signal to the power and control systemto provide feedback to the user.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to the user.While the drive mechanisms of the present disclosure are described withreference to the gear assembly and regulating mechanism shown in thefigures, a range of configurations may be acceptable and capable ofbeing employed within the embodiments of the present disclosure, aswould readily be appreciated by an ordinarily skilled artisan.Accordingly, the embodiments of the present disclosure are not limitedto the specific gear assembly and regulating mechanism described herein,which is provided as an exemplary embodiment of such mechanisms foremployment within the controlled delivery drive mechanisms and drugdelivery pumps.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on the patient's activitylevel, heart rate, blood sugar level, blood pressure, etc. As above,these measurements may be used to determine the need for a bolusinjection or for the increase or decrease of the basal injectiondelivery rate or adjustment to the basal injection delivery profile. Inat least one embodiment, these input measurements may be monitored bythe device itself. Additionally, or alternatively, they may be monitoredby a secondary device such as a smart-phone, smart watch, heart ratemonitor, glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of actuator 90101. The change in the rate of movementof actuator 90101 causes a change in the rotation rate of regulatingmechanism 90500 which, in turn, controls the rate of drug delivery tothe user. Alternatively, the delivery profile may be altered by a changein the characteristics of the flow path of medicament through theconduit connecting the drug container and insertion mechanism. Thechange may be caused by the introduction, removal, or modification of aflow restrictor which restricts flow of medicament from the drugcontainer to the insertion mechanism. For example, a flow restrictor mayhave multiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the user. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the multi-function drive mechanism and/or the drugdelivery device.

Assembly and/or manufacturing of controlled delivery drive mechanism90100, drug delivery pump 9010, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9050 may first be assembledand filled with a fluid for delivery to the user. The drug container9050 includes a cap 9052, a pierceable seal 9056, a barrel 9058, and aplunger seal 9060. The pierceable seal 9056 may be fixedly engagedbetween the cap 9052 and the barrel 9058, at a distal end of the barrel9058. The barrel 9058 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9060 from theproximal end of the barrel 9058. An optional connection mount 9054 maybe mounted to a distal end of the pierceable seal 9056. The connectionmount 9054 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9058 of the drug container 9050. Thedrug container 9050 may then be mounted to a distal end of drive housing90130.

One or more drive biasing members 90122 may be inserted into a distalend of the drive housing 90130. Optionally, a cover sleeve 90140 may beinserted into a distal end of the drive housing 90130 to substantiallycover biasing member 90122. A piston may be inserted into the distal endof the drive housing 90130 such that it resides at least partiallywithin an axial pass-through of the biasing member 90122 and the biasingmember 90122 is permitted to contact a piston interface surface 90110Cof piston 90110A, 90110B at the distal end of the biasing member 90122.An optional cover sleeve 90140 may be utilized to enclose the biasingmember 122 and contact the piston interface surface 90110C of piston90110A, 90110B. The piston 90110A, 90110B and drive biasing member90122, and optional cover sleeve 90140, may be compressed into drivehousing 90130. Such assembly positions the drive biasing member 90122 inan initial compressed, energized state and preferably places a pistoninterface surface 90110C in contact with the proximal surface of theplunger seal 9060 within the proximal end of barrel 9058. The piston,piston biasing member, contact sleeve, and optional components, may becompressed and locked into the ready-to-actuate state within the drivehousing 90130 prior to attachment or mounting of the drug container9050. The tether 90525 is pre-connected to the proximal end of thepiston 90110A, 90110B and passed through the axial aperture of thebiasing member 90122 and drive mechanism 90130, and then wound throughthe interior of the drug delivery device with the other end of thetether 90525 wrapped around the winch drum/gear 90520 of the regulatingmechanism 90500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the body of a user. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device, as shown in FIG. 69B.

Certain optional standard components or variations of drive mechanism90100 or drug delivery device 9010 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9018 to enablethe user to view the operation of the drug delivery device 9010 orverify that drug dose has completed. Similarly, the drug delivery device9010 may contain an adhesive patch 9026 and a patch liner 9028 on thebottom surface of the housing 9012. The adhesive patch 9026 may beutilized to adhere the drug delivery device 9010 to the body of the userfor delivery of the drug dose. As would be readily understood by onehaving ordinary skill in the art, the adhesive patch 9026 may have anadhesive surface for adhesion of the drug delivery device to the body ofthe user. The adhesive surface of the adhesive patch 9026 may initiallybe covered by a non-adhesive patch liner 9028, which is removed from theadhesive patch 9026 prior to placement of the drug delivery device 9010in contact with the body of the user. Removal of the patch liner 9028may further remove the sealing membrane 90254 of the insertion mechanism90200, opening the insertion mechanism to the body of the user for drugdelivery (as shown in FIG. 69C).

Similarly, one or more of the components of controlled delivery drivemechanism 90100 and drug delivery device 9010 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9010 is shown as two separate components upper housing9012A and lower housing 9012B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The novel controlleddelivery drive mechanisms of the present disclosure may be directly orindirectly activated by the user. Furthermore, the novel configurationsof the controlled delivery drive mechanism and drug delivery devices ofthe present disclosure maintain the sterility of the fluid pathwayduring storage, transportation, and through operation of the device.Because the path that the drug fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe drug container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent disclosure do not require terminal sterilization upon completionof assembly.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connection, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the body of a user, wherein aregulating mechanism acting to restrain the distribution of a tether isutilized to meter the free axial translation of the piston. The methodof operation of the drive mechanism and the drug delivery device may bebetter appreciated with reference to FIGS. 70A-70D and FIGS. 71A-71D, asdescribed above.

XVIII. Additional Embodiments of Multi-Function Drive Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 69A-75B, 80A-85C, 86A-91, 92A-99, and 100A-109B may beconfigured to incorporate the embodiments of the drive mechanismdescribed below in connection with FIGS. 110A-141B. The embodiments ofthe drive mechanism described below in connection with FIGS. 110A-141Bmay be used to replace, in its entirety or partially, theabove-described drive mechanism 100, 6100, 8100, 90100, 92100, 93100,94100, or 95100, or any other drive mechanism described herein, whereappropriate.

The present disclosure provides drive mechanisms for the controlleddelivery of drug substances, controlled drug delivery pumps with suchdrive mechanisms, the methods of operating such devices, and the methodsof assembling such devices. Notably, the drive mechanisms of the presentdisclosure enable or initiate several functions, including: (i)controlling the rate of drug delivery by metering, providing resistance,or otherwise preventing free axial translation of the plunger sealutilized to force a drug substance out of a drug container; (ii)triggering a needle insertion mechanism to provide a fluid pathway fordrug delivery to a target; and (iii) connecting a sterile fluid pathwayto a drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the target. The novelembodiments of the present disclosure thus are capable of deliveringdrug substances at variable rates. The drive mechanisms of the presentdisclosure may be pre-configurable or dynamically configurable, such asby control by the power and control system, to meet desired deliveryrates or profiles, as explained in detail below. Additionally, the drivemechanisms of the present disclosure provide integrated statusindication features which provide feedback to the user before, during,and after drug delivery. For example, the user may be provided aninitial feedback to identify that the system is operational and readyfor drug delivery. Upon activation, the system may then provide one ormore drug delivery status indications to the user. At completion of drugdelivery, the drive mechanism and drug delivery device may provide anend-of-dose indication. Because the end-of-dose indication is related tothe physical end of axial translation and/or travel of one or morecomponents of the drive mechanism, the drive mechanism and drug deliverydevice provide a true end-of-dose indication to the user. Through thesemechanisms, confirmation of drug dose delivery can accurately beprovided to the user or administrator. Accordingly, the novel devices ofthe present disclosure alleviate one or more of the problems associatedwith prior art devices, such as those referred to above.

In a first embodiment, the present disclosure provides a drive mechanismwhich includes an actuator, a gear assembly including a main gear, adrive housing, and a drug container having a cap, a pierceable seal (notvisible), a barrel, and a plunger seal. The main gear may be, forexample, a star gear disposed to contact multiple secondary gears orgear surfaces. A drug chamber, located within the barrel between thepierceable seal and the plunger seal, may contain a drug fluid fordelivery through the insertion mechanism and drug delivery device intothe target. A piston, and one or more biasing members, wherein the oneor more biasing members are initially retained in an energized state andis configured to bear upon an interface surface of the piston, may alsobe incorporated in the drive mechanism. The piston is configured totranslate substantially axially within a drug container having a plungerseal and a barrel. A tether is connected at one end to the piston and atanother end to a winch assembly of a regulating mechanism, wherein thetether restrains the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon. The drug container may containa drug fluid within a drug chamber for delivery to a target. Optionally,a cover sleeve may be utilized between the biasing member and theinterface surface of the piston to hide the interior components of thebarrel (namely, the piston and the biasing member) from view duringoperation of the drive mechanism. The tether is configured to bereleased from a winch assembly of a regulating mechanism of the drivemechanism to meter the free expansion of the biasing member from itsinitial energized state and the free axial translation of the pistonupon which the biasing member bears upon.

Alternatively, the present disclosure provides a drive mechanism forutilization with a drug container in a drug delivery device, the drugcontainer including a barrel and a plunger seal, including a tether, anelectrical actuator, and a gear interface. Rotation of the gearinterface is controlled by the electrical actuator. A gear assembly isin rotational engagement with the gear interface and includes a maingear and a regulating mechanism, wherein release of the tether ismetered by operation of the gear assembly through the regulatingmechanism. A drive housing is provided. A piston is connected to thetether and configured for disposition in the barrel adjacent the plungerseal. The piston is configured to translate substantially axially withinthe drug container and a biasing member is configured for disposition atleast partially within the barrel, the biasing member being retained inan energized state between the piston and drive housing. The release ofthe tether controls the free expansion of the biasing member from itsenergized state and the free axial translation of the piston upon whichthe biasing member bears upon.

The present disclosure provides in other aspects a drug delivery pump,including a drive mechanism of any of the disclosed embodiments and adrug container including a barrel and a plunger seal, a needle insertionmechanism and a fluid pathway connector. The disclosure also may providea safety mechanism configured to terminate or slow delivery of the drugfluid through the fluid pathway connector upon a loss of tension in thetether.

In yet another embodiment, the present disclosure provides a primabledrive mechanism for utilization with a drug container in a drug deliverydevice, the drug container including a barrel and a plunger seal,including a tether, a drive housing, and a winch drum. A piston isconnected to the tether and configured for disposition in the barreladjacent the plunger seal, the piston configured to translatesubstantially axially within the drug container and a biasing member isconfigured for disposition at least partially within the barrel, thebiasing member being retained in an energized state between the pistonand drive housing. The tether is disposed and wound upon the winch drumand is configured to be released from the winch drum by rotation of thewinch drum to meter the free expansion of the biasing member from itsenergized state and the free axial translation of the piston upon whichthe biasing member bears upon.

In at least one embodiment of the present disclosure, the regulatingmechanism is a gear assembly driven by an actuator of the drivemechanism. The regulating mechanism retards or restrains thedistribution of the tether, only allowing it to advance at a regulatedor desired rate. This restricts movement of the piston within thebarrel, which is pushed by one or more biasing members, hencecontrolling the movement of the plunger seal and delivery of the drugcontained in the chamber. As the plunger seal advances in the drugcontainer, the drug substance is dispensed through the sterile pathwayconnection, conduit, insertion mechanism, and into the target for drugdelivery. The actuator may be a number of power/motion sourcesincluding, for example, a motor (e.g., a DC motor, AC motor, or steppermotor) or a solenoid (e.g., linear solenoid, rotary solenoid). In aparticular embodiment, the actuator is a rotational stepper motor with anotch that corresponds with the gear teeth of the main/star gear.

The regulating mechanism may further include one or more gears of a gearassembly. One or more of the gears may be, for example, compound gearshaving a small diameter gear attached at a shared center point to alarge diameter gear. The gear assembly may include a gear coupled to awinch assembly upon which the tether may be releasably wound.Accordingly, rotation of the gear assembly initiated by the actuator maybe coupled to winch assembly (i.e., through the gear assembly), therebycontrolling the distribution of the tether, the rate of expansion of thebiasing members and the axial translation of the piston, and the rate ofmovement of the plunger seal within the barrel to force a fluid from thedrug chamber. The rotational movement of the winch assembly, and thusthe axial translation of the piston and plunger seal, are metered,restrained, or otherwise prevented from free axial translation by othercomponents of the regulating element, as described herein. Notably, theregulating mechanisms of the present disclosure do not drive thedelivery of fluid substances from the drug chamber. The delivery offluid substances from the drug chamber is caused by the expansion of thebiasing member from its initial energized state acting upon the pistonand plunger seal. The regulating mechanisms instead function to provideresistance to the free motion of the piston and plunger seal as they arepushed by the expansion of the biasing member from its initial energizedstate. The regulating mechanism does not drive the delivery but onlycontrols the delivery motion. The tether limits or otherwise restrainsthe motion of the piston and plunger seal, but does not apply the forcefor the delivery.

In addition to controlling the rate of drug delivery by metering,providing resistance, or otherwise preventing free axial translation ofthe plunger seal utilized to force a drug substance out of a drugcontainer (thereby delivering drug substances at variable rates and/ordelivery profiles); the drive mechanisms of the present disclosure mayconcurrently or sequentially perform the steps of: triggering a needleinsertion mechanism (NIM) to provide a fluid pathway for drug deliveryto a target; and connecting a sterile fluid pathway to a drug containerto permit fluid flow from the drug container to the needle insertionmechanism for delivery to the target. In at least one embodiment,initial motion by the actuator of the drive mechanism causes rotation ofthe main/star gear. In one manner, the main/star gear conveys motion tothe regulating mechanism through the gear assembly. In another manner,the main/star gear conveys motion to the needle insertion mechanismthrough a gear. As the gear is rotated by the main/star gear, the gearengages the needle insertion mechanism to initiate the fluid pathwayconnector into the target, as described in detail above. In oneparticular embodiment, the needle insertion mechanism is a rotationalneedle insertion mechanism. Accordingly, the gear is configured toengage a corresponding gear surface of the needle insertion mechanism.Rotation of gear causes rotation of needle insertion mechanism throughthe gear interaction between gear of the drive mechanism andcorresponding gear surface of the needle insertion mechanism. Oncesuitable rotation of the needle insertion mechanism occurs, the needleinsertion mechanism may be initiated to create the fluid pathwayconnector into the target, as described in detail herein.

In another embodiment, the drive mechanism may configure a NIMactivation mechanism for activation by a user. For example, the NIMactivation mechanism may be in an initial configuration in whichdepression of an actuation of an activation mechanism does not activatethe NIM. The drive mechanism may subsequently transform the NIMactivation mechanism to a configuration in which actuation of theactivation mechanism does activate needle insertion. For example,actuation of the activation mechanism may cause translation of a slide.The drive mechanism may cause a selector member to be positioned suchthat contact between the slide and the selector member causes at least aportion of the slide to be displaced. This displacement brings the slideinto contact with a throw arm which is caused to translate with theslide. This translation of the throw arm causes activation of needleinsertion. For example, the throw arm may cause displacement of a NIMinterlock which, in an initial configuration, prevents rotation of a NIMretainer. The NIM retainer initially prevents activation of needleinsertion. After translation of the NIM interlock, an aperture of theNIM interlock is aligned with a portion of the NIM retainer, allowingrotation of the NIM retainer. This rotation allows activation of needleinsertion.

In at least one embodiment, rotation of the needle insertion mechanismin this manner may also cause a connection of a sterile fluid pathway toa drug container to permit fluid flow from the drug container to theneedle insertion mechanism for delivery to the target. Ramp aspect ofneedle insertion mechanism is caused to bear upon a movable connectionhub of the sterile fluid pathway connector. As the needle insertionmechanism is rotated by the drive mechanism, a ramp aspect of the needleinsertion mechanism bears upon and translates a movable connection hubof the sterile fluid pathway connector to facilitate a fluid connectiontherein. In at least one embodiment, the needle insertion mechanism maybe configured such that a particular degree of rotation enables theneedle/trocar to retract as detailed above. Additionally oralternatively, such needle/trocar retraction may be configured to occurupon a user-activity or upon movement or function of another componentof the drug delivery device. In at least one embodiment, needle/trocarretraction may be configured to occur upon end-of-drug-delivery, astriggered by, for example, the regulating mechanism and/or one or moreof the status readers as described herein.

In yet another embodiment, the drive mechanism may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In a further embodiment, the present disclosure provides a drug deliverypump with controlled drug delivery. The drug delivery pump having ahousing and an assembly platform, upon which an activation mechanism, aninsertion mechanism, a fluid pathway connector, a power and controlsystem, and a controlled delivery drive mechanism may be mounted, saiddrive mechanism having a drive housing, a piston, and a biasing member,wherein the biasing member is initially retained in an energized stateand is configured to bear upon an interface surface of the piston. Thepiston is configured to translate substantially axially within a drugcontainer having a plunger seal and a barrel. A tether is connected atone end to the piston and at another end to a winch assembly of adelivery regulating mechanism, wherein the tether restrains the freeexpansion of the biasing member from its initial energized state and thefree axial translation of the piston upon which the biasing member bearsupon. The drug container may contain a drug fluid within a drug chamberfor delivery to a target. Optionally, a cover sleeve may be utilizedbetween the biasing member and the interface surface of the piston tohide the interior components of the barrel (namely, the piston and thebiasing member) from view during operation of the drive mechanism. Thetether is configured to be released from a winch assembly of thedelivery regulating mechanism to meter the free expansion of the biasingmember from its initial energized state and the free axial translationof the piston upon which the biasing member bears upon.

In another embodiment, the drug delivery device further includes a gearassembly. The gear assembly may include a winch gear connected to awinch assembly upon which the tether may be releasably wound, rotationof the winch assembly releases the tether from the winch assembly tometer the free expansion of the biasing member from its initialenergized state and the free axial translation of the piston upon whichthe biasing member bears upon. The metering of the tether controls therate or profile of drug delivery to a target. The piston may be one ormore parts and connects to a distal end of the tether. The winchassembly is coupled to a regulating mechanism which controls rotation ofthe winch assembly and hence metering of the translation of the piston.

In yet another embodiment, the drug delivery device may include a statusreader configured to read or recognize one or more corresponding statustriggers. The status triggers may be incrementally spaced on the tether,wherein, during operation of the drive mechanism, interaction betweenthe status reader and the status triggers transmit a signal to a powerand control system to provide feedback to a user. The status reader maybe an optical status reader and the corresponding status triggers areoptical status triggers, an electromechanical status reader and thecorresponding status triggers are electromechanical status triggers, ora mechanical status reader and the corresponding status triggers aremechanical status triggers.

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether by the winch assembly and thereby permit axial translationof the piston by the biasing member to translate a plunger seal within abarrel. The one or more inputs may be provided by the actuation of theactivation mechanism, a control interface, and/or a remote controlmechanism. The power and control system may be configured to receive oneor more inputs to adjust the restraint provided by the tether and winchassembly on the free axial translation of the piston upon which thebiasing member bears upon to meet a desired drug delivery rate orprofile, to change the dose volume for delivery to the target, and/or tootherwise start, stop, or pause operation of the drive mechanism.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is delivered,often irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on activity level, heartrate, blood sugar level, blood pressure, etc. As above, thesemeasurements may be used to determine the need for a bolus injection orfor the increase or decrease of the basal injection delivery rate oradjustment to the basal injection delivery profile. In at least oneembodiment, these input measurements may be monitored by the deviceitself. Additionally, or alternatively, they may be monitored by asecondary device such as a smart-phone, smart watch, heart rate monitor,glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of the actuator. The change in the rate of movement ofthe actuator causes a change in the rotation rate of the regulatingmechanism which, in turn, controls the rate of drug delivery to thetarget. Alternatively, the delivery profile may be altered by a changein the characteristics of the flow path of medicament through theconduit connecting the drug container and insertion mechanism. Thechange may be caused by the introduction, removal, or modification of aflow restrictor which restricts flow of medicament from the drugcontainer to the insertion mechanism. For example, a flow restrictor mayhave multiple flow paths which may be selectively placed in fluidcommunication with an input and an output of the flow restrictor. Byproviding flow paths which are of different length or cross-section therate of delivery may be controlled. In other embodiments, the deliveryprofile may be altered by the introduction or removal of an impingementof the conduit. An impingement of the flow path may interrupt or slowflow of medicament through the conduit, thereby controlling the rate ofdelivery to the target. Accordingly, one or more embodiments of thepresent disclosure are capable of producing a change to the rate ofmedicament delivery from the drug container thereby providing a dynamiccontrol capability to the drive mechanism and/or the drug deliverydevice.

The devices described herein may further include features which preventthe delivery of an excess volume of medicament or delivery at too rapidof a rate, e.g., to prevent a run-away condition of uncontrolled orundesired delivery of the medicament. By providing such automatic safetymechanisms, the safety of the target may be ensured. Some medicaments,such as insulin or other treatments for diabetes, can be dangerous, andpotentially even deadly, if they are not delivered according toprescribed parameters. Such safety mechanisms can include a brakemechanism, a plunger seal piercing mechanism, and a plunger sealdisplacing mechanism, such as those described in detail herein. Thesafety features described below may ensure that delivery of themedicament is terminated if delivery deviates from the specifiedparameters.

The present disclosure provides drive mechanisms for the delivery ofdrug substances and drug delivery pumps which incorporate such drivemechanisms. The drive mechanisms of the present disclosure may enable orinitiate one or more functions, including: (i) controlling the rate ofdrug delivery by metering, providing resistance, or otherwise preventingfree axial translation of the plunger seal utilized to force a drugsubstance out of a drug container; (ii) triggering a needle insertionmechanism to provide a fluid pathway for drug delivery to a target; and(iii) connecting a sterile fluid pathway to a drug container to permitfluid flow from the drug container to the needle insertion mechanism fordelivery to the target. The drive mechanisms of the present disclosurecontrol the rate of drug delivery by metering, providing resistance, orotherwise preventing free axial translation of the plunger seal utilizedto force a drug substance out of a drug container and, thus, are capableof delivering drug substances at variable rates and/or deliveryprofiles. Additionally, the drive mechanisms of the present disclosureprovide integrated status indication features which provide feedback tothe user before, during, and after drug delivery. For example, the usermay be provided an initial feedback to identify that the system isoperational and ready for drug delivery. Upon activation, the system maythen provide one or more drug delivery status indications to the user.At completion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication.

The devices described herein may be configured for delivery ofcontrolled substances and may further include features that preventso-called “run-away” delivery of medicament. When delivering controlledsubstances, this may be an important safety feature to protect thetarget. For example, some medicaments, such as insulin, can bedangerous, and potentially even deadly, when administered in too large aquantity and/or at too rapid of a rate. By providing such automaticsafety stop mechanisms, the safety of the target may be ensured.

The novel devices of the present disclosure provide drive mechanismswith integrated status indication and drug delivery pumps whichincorporate such drive mechanisms. Such devices are safe and easy touse, and are aesthetically and ergonomically appealing. The devicesdescribed herein incorporate features which make activation, operation,and lock-out of the device simple for even untrained users. The noveldevices of the present disclosure provide these desirable featureswithout any of the problems associated with known prior art devices.Certain non-limiting embodiments of the novel drug delivery pumps, drivemechanisms, and their respective components are described further hereinwith reference to the accompanying figures.

As used herein, the terms “pump” and “delivery device” are intended toinclude any number of drug delivery systems which are capable ofdispensing a fluid to a user upon activation. Such drug delivery systemsinclude, but are not limited to, for example, injection systems,infusion pumps, bolus injectors, on-body injectors, and the like. FIGS.110A-111A show an exemplary drug delivery device according to at leastone embodiment of the present disclosure. FIGS. 110B and 111A show thedrug delivery device with the top housing removed so that the internalcomponents are visible. The drug delivery device may be utilized toadminister delivery of a drug treatment into a target. As shown in FIGS.110A-110C, the drug delivery device 9610 includes a pump housing 9612.Pump housing 9612 may include one or more housing subcomponents whichare fixedly engageable to facilitate easier manufacturing, assembly, andoperation of the drug delivery device. For example, drug delivery device9610 includes a pump housing 9612 which may include an upper housing9612A and a lower housing 9612B. The pump housing 9612 may include oneor more tamper evidence features to identify if the drug delivery devicehas been opened or tampered with. For example, the pump housing 9612 mayinclude one or more tamper evidence labels or stickers, such as labelsthat bridge across the upper housing and the lower housing. Additionallyor alternatively, the housing 9612 may include one or more snap arms orprongs connecting between the upper housing and the lower housing. Abroken or altered tamper evidence feature would signal to the user, thephysician, the supplier, the manufacturer, or the like, that the drugdelivery device has potentially been tampered with, e.g., by accessingthe internal aspects of the device, so that the device is evaluated andpossibly discarded without use by or risk to the user. The drug deliverydevice may further include an activation mechanism 9614, a statusindicator (not shown), and a window 9618. The window 9618 may be anytranslucent or transmissive surface through which the operation of thedrug delivery device may be viewed. As shown in FIGS. 110B and 111A,drug delivery device 9610 further includes assembly platform 9620, drivemechanism 96100 having drug container 9650, insertion mechanism 96200,fluid pathway connector 96300, and a power and control system 96400. Oneor more of the components of such drug delivery devices may be modularin that they may be, for example, pre-assembled as separate componentsand configured into position onto the assembly platform 9620 of the drugdelivery device 9610 during manufacturing.

The pump housing 9612 contains all of the device components and providesa means of removably attaching the device 9610 to the target. The pumphousing 9612 also provides protection to the interior components of thedevice 9610 against environmental influences. The pump housing 9612 isergonomically and aesthetically designed in size, shape, and relatedfeatures to facilitate easy packaging, storage, handling, and use byusers who may be untrained and/or physically impaired. Furthermore, theexternal surface of the pump housing 9612 may be utilized to provideproduct labeling, safety instructions, and the like. Additionally, asdescribed above, housing 9612 may include certain components, such asone or more status indicators and windows, which may provide operationfeedback to the user.

In at least one embodiment, the drug delivery device 9610 provides anactivation mechanism 14 that is displaced by the user to trigger thestart command to the power and control system. In a preferredembodiment, the activation mechanism 9614 is a start button that islocated through the pump housing 9612, such as through an aperturebetween upper housing 9612A and lower housing 9612B, and which contactseither directly or indirectly the power and control system 96400. In atleast one embodiment, the start button may be a push button, and inother embodiments, may be an on/off switch, a toggle, or any similaractivation feature known in the art. The pump housing 9612 also providesone or more status indicators and windows. In other embodiments, one ormore of the activation mechanism 9614, the status indicator, the window9618, and combinations thereof may be provided on the upper housing9612A or the lower housing 9612B such as, for example, on a side visibleto the user when the drug delivery device 9610 is placed on the target.Housing 9612 is described in further detail hereinafter with referenceto other components and embodiments of the present disclosure.

Drug delivery device 9610 is configured such that, upon activation by auser by depression of the activation mechanism, the drive mechanism isactivated to perform one or more of the following functions: insert afluid pathway into the target; enable, connect, or open necessaryconnections between a drug container, a fluid pathway, and a sterilefluid conduit; and force drug fluid stored in the drug container throughthe fluid pathway and fluid conduit for delivery into a target. In atleast one embodiment, such delivery of drug fluid into a target isperformed by the drive mechanism in a controlled manner. One or moreoptional safety mechanisms may be utilized, for example, to preventpremature activation of the drug delivery device. For example, anoptional on-body sensor 9624 may be provided in one embodiment as asafety feature to ensure that the power and control system, or theactivation mechanism, cannot be engaged unless the drug delivery device9610 is in contact with the target. In one such embodiment, the on-bodysensor is located on the bottom of lower housing 9612B where it may comein contact with the target. Upon displacement or activation of theon-body sensor 9624, depression of the activation mechanism ispermitted. Accordingly, in at least one embodiment the on-body sensor isa mechanical safety mechanism, such as for example a mechanical lockout, that prevents triggering of the drug delivery device 9610 by theactivation mechanism. In another embodiment, the on-body sensor may bean electro-mechanical sensor such as a mechanical lock out that sends asignal to the power and control system to permit activation. In stillother embodiments, the on-body sensor can be electrically based such as,for example, a conductive, capacitive- or impedance-based sensor whichmust detect tissue before permitting activation of the power and controlsystem. In at least one embodiment, housing 9612 is configured to atleast partially prevent harmful matter from entering the drug deliverydevice. For example, the housing may be configured to restrict thepassage of fluids into the drug delivery device. This may allow thedevice to be worn in the shower, while swimming, or during otheractivities. Use of an electrically based on-body sensor may eliminatepotential points of entry into the drug delivery device for such fluids.These concepts are not mutually exclusive and one or more combinationsmay be utilized within the breadth of the present disclosure to prevent,for example, premature activation of the drug delivery device. In apreferred embodiment, the drug delivery device 9610 utilizes one or moreelectrically based on-body sensors. Additional integrated safetymechanisms are described herein with reference to other components ofthe novel drug delivery devices.

XVIII.A. Power and Control System:

The power and control system may include a power source, which providesthe energy for various electrical components within the drug deliverydevice, one or more feedback mechanisms, a microcontroller, a circuitboard, one or more conductive pads, and one or more interconnects. Othercomponents commonly used in such electrical systems may also beincluded, as would be appreciated by one having ordinary skill in theart. The one or more feedback mechanisms may include, for example,audible alarms such as piezo alarms and/or light indicators such aslight emitting diodes (LEDs). The microcontroller may be, for example, amicroprocessor. The power and control system controls several deviceinteractions with the user and interfaces with the drive mechanism96100. In one embodiment, the power and control system interfaces eitherdirectly or indirectly with an on-body sensor 9624 to identify when thedevice is in contact with the target and/or the activation mechanism9614 to identify when the device has been activated. The power andcontrol system may also interface with the status indicator of the pumphousing 9612, which may be a transmissive or translucent material whichpermits light transfer, to provide visual feedback to the user. Thepower and control system interfaces with the drive mechanism 96100through one or more interconnects to relay status indication, such asactivation, drug delivery, and end-of-dose, to the user. Such statusindication may be presented to the user via auditory tones, such asthrough the audible alarms, and/or via visual indicators, such asthrough the LEDs. In a preferred embodiment, the control interfacesbetween the power and control system and the other components of thedrug delivery device are not engaged or connected until activation bythe user. This is a desirable safety feature that prevents accidentaloperation of the drug delivery device and may additionally maintain theenergy contained in the power source during storage, transportation, andthe like.

The power and control system may be configured to provide a number ofdifferent status indicators to the user. For example, the power andcontrol system may be configured such that after the on-body sensorand/or trigger mechanism have been pressed, the power and control systemprovides a ready-to-start status signal via the status indicator ifdevice start-up checks provide no errors. After providing theready-to-start status signal and, in an embodiment with the optionalon-body sensor, if the on-body sensor remains in contact with thetarget, the power and control system will power the drive mechanism96100 to begin delivery of the drug treatment through the fluid pathwayconnector 96300 and sterile fluid conduit (not shown).

Additionally, the power and control system may be configured to identifyremoval of the drug delivery device from its packaging. The power andcontrol system may be mechanically, electronically, orelectro-mechanically connected to the packaging such that removal of thedrug delivery device from the packaging may activate or power-on thepower and control system for use, or simply enable the power and controlsystem to be powered-on by the user. In such an embodiment, withoutremoval of the drug delivery device from the packaging the drug deliverydevice cannot be activated. This provides an additional safety mechanismof the drug delivery device and for the user. In at least oneembodiment, the drug delivery device or the power and control system maybe electronically or electro-mechanically connected to the packaging,for example, such as by one or more interacting sensors from a range of:Hall effect sensors; giant magneto resistance (GMR) or magnetic fieldsensors; optical sensors; capacitive or capacitance change sensors;ultrasonic sensors; and linear travel, LVDT, linear resistive, orradiometric linear resistive sensors; and combinations thereof, whichare capable of coordinating to transmit a signal between components toidentify the location there-between. Additionally or alternatively, thedrug delivery device or the power and control system may be mechanicallyconnected to the packaging, such as by a pin and slot relationship whichactivates the system when the pin is removed (i.e., once the drugdelivery device is removed from the packaging).

In a preferred embodiment of the present disclosure, once the power andcontrol system has been activated, the drive mechanism is initiated toperform one or more of the steps of actuating the insertion mechanism96200 and the fluid pathway connector 96300, while also permitting thedrug fluid to be forced from the drug container. During the drugdelivery process, the power and control system is configured to providea dispensing status signal via the status indicator. After the drug hasbeen administered into the target and after the end of any additionaldwell time, to ensure that substantially the entire dose has beendelivered to the target, the power and control system may provide anokay-to-remove status signal via the status indicator. This may beindependently verified by the user by viewing the drive mechanism anddrug dose delivery through the window 9618 of the pump housing 9612.Additionally, the power and control system may be configured to provideone or more alert signals via the status indicator, such as for examplealerts indicative of fault or operation failure situations.

The power and control system may additionally be configured to acceptvarious inputs from the user to dynamically control the drive mechanisms96100 to meet a desired drug delivery rate or profile. For example, thepower and control system may receive inputs, such as from partial orfull activation, depression, and/or release of the activation mechanism,to set, initiate, stop, or otherwise adjust the control of the drivemechanism 96100 via the power and control system to meet the desireddrug delivery rate or profile. Similarly, the power and control systemmay be configured to do one or more of the following: receive suchinputs to adjust the drug dose volume; to prime the drive mechanism,fluid pathway connector, and fluid conduit; and/or to start, stop, orpause operation of the drive mechanism 96100. Such inputs may bereceived by the user directly acting on the drug delivery device 9610,such as by use of the activation mechanism 9614 or a different controlinterface, or the power and control system may be configured to receivesuch inputs from a remote control device. Additionally or alternatively,such inputs may be pre-programmed.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to theuser. Similarly, activation of the device may require a delayeddepression (i.e., pushing) of the activation mechanism of the drugdelivery device 9610 prior to drug delivery device activation.Additionally, the system may include a feature which permits the user torespond to the end-of-dose signals and to deactivate or power-down thedrug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

Additionally, the power and control system may be configured to maintainregulation of the system's power source while providing momentary powerto an actuator. During operation of the drug delivery device, as will bedescribed further herein, momentary power is needed to move an actuatorclockwise and counterclockwise between mechanical limits. This motioncontrols the motion of the drive system and, hence, the rate of deliveryof the medicament. Directly supplying power to the actuator may lead toa large voltage drop which could interrupt the power source to othercomponents of the drug delivery device. To avoid this, the power andcontrol system may be configured to decouple the power source from theactuator when power is supplied to the actuator. To this end, the powerand control system may include a switching device, such as afield-effect transistor; a charge-slowing device, such as a resistor;and a storage device, such as a capacitor. The three devices areserially connected between the power source and ground. The output isobtained from the capacitor and is connected to the actuator via acontrol device, such as an H-bridge. During operation the systemoperates in the following manner: First, the switching device is set toa fully closed configuration, connecting the power source, to thestorage device and allowing the storage device to be charged by thepower source in a length of time defined by, for example, the RC timeconstant. Second, the switch is opened, thereby disconnecting the powersource from the storage device with the storage device remaining fullycharged. Third, the charged storage device is applied to the controldevice. Fourth, the control device applies the stored power to theactuator and controls the actuator direction (clockwise orcounterclockwise). In this way, the power source is not connected to theactuator when the actuator is powered, ensuring that the power sourcedoes not experience a voltage drop. This process repeats as needed toprovide continued actuator clockwise and counterclockwise inputs to thepump drive mechanism without collapsing the system power source.

XVIII.B. Insertion Mechanism:

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a target, for example, through any suitable hollowtubing. A hollow needle or a solid bore needle may be used to pierce thetarget and place a hollow cannula at the appropriate delivery position,with the needle being at least partially removed or retracted prior todrug delivery to the target. As stated above, the fluid can beintroduced into the body through any number of means, including but notlimited to: an automatically inserted needle, cannula, micro-needlearray, or infusion set tubing. A number of mechanisms may also beemployed to activate the needle insertion into the target. For example,a biasing member such as a spring may be employed to provide sufficientforce to cause the needle and cannula to pierce the target. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the target. In one embodiment, theinsertion mechanism may generally be as described in InternationalPatent Application No. PCT/US2012/53174, which is included by referenceherein in its entirety for all purposes. Such a configuration may beutilized for insertion of the drug delivery pathway into, or below, thetarget in a manner that minimizes pain. Other known methods forinsertion of a fluid pathway may be utilized and are contemplated withinthe bounds of the present disclosure, including a rigid needle insertionmechanism and/or a rotational needle insertion mechanism as developed bythe assignee of the present disclosure.

In at least one embodiment, the insertion mechanism 96200 includes aninsertion mechanism housing that may have a base for connection to theassembly platform and/or pump housing (as shown in FIG. 110B and FIG.110C). The connection of the base to the assembly platform 9620 may be,for example, such that the bottom of the base is permitted topass-through a hole in the assembly platform to permit direct contact ofthe base to the target. In such configurations, the bottom of the basemay include a sealing membrane that is removable prior to use of thedrug delivery device 9610. The insertion mechanism may further includeone or more insertion biasing members, a needle, a retraction biasingmember, a cannula, and a manifold. The manifold may connect to a sterilefluid conduit to permit fluid flow through the manifold, cannula, andinto the target during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as a “trocars.” In some embodiments, the needle is a 9627gauge solid core trocar and in other embodiments, the needle may be anysize needle suitable to insert the cannula for the type of drug and drugadministration (e.g., subcutaneous, intramuscular, intradermal, etc.)intended. In one or more embodiments, the insertion mechanism maygenerally be as described in International Patent Application No.PCT/US2012/53174 published as WO 2013/033421 A2, International PatentApplication No. PCT/US2012/053241 published as WO 2013/033467 A2 orInternational Patent Application No. PCT/US2015/052815, which areincluded by reference herein in their entirety for all purposes.

The base includes a base opening through which the needle and cannulamay pass-through during operation of the insertion mechanism. Sterilityof the cannula and needle are maintained by their initial positioningwithin the sterile portions of the insertion mechanism. The base openingof base may be closed from non-sterile environments as well, such as byfor example a sealing membrane.

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. Displacement of the lockoutpin(s), by one or more methods such as pulling, pushing, sliding, and/orrotation, permits insertion biasing member to decompress from itsinitial compressed, energized state. This decompression of the insertionbiasing member drives the needle and, optionally, the cannula into thetarget. At the end of the insertion stage or at the end of drug delivery(as triggered by the drive mechanism), the retraction biasing member ispermitted to expand in the proximal direction from its initial energizedstate. This axial expansion in the proximal direction of the retractionbiasing member retracts the needle. If an inserter needle/trocar andcannula configuration is utilized, retraction of the needle may occurwhile maintaining the cannula in fluid communication with the target.Accordingly, the insertion mechanism may be used to insert a needle andcannula into the target and, subsequently, retract the needle whileretaining the cannula in position for drug delivery to the target.

In one or more embodiments, the insertion mechanism may generally be asdescribed in International Patent Application No. PCT/US2016/017534filed Feb. 10, 2016, which is included by reference herein in itsentirety for all purposes. In at least one embodiment, as shown in FIG.115A, the insertion mechanism includes a rotationally biased member96210 which is initially held in an energized state. In a preferredembodiment, the rotationally biased member is a torsional spring. Therotational biasing member may be prevented from de-energizing byinteraction of gear surface 96208 with gear 96112 as shown in FIG. 111Aor, alternatively, by contact of a component of the insertion mechanismwith a rotation prevention feature of the drug delivery device, asdescribed further herein. Upon activation of the device, or anotherinput, the rotationally biased member 96210 is permitted to, at leastpartially, de-energize. This causes one or more components of theinsertion mechanism to rotate and, in turn, cause, or allow, theinsertion of the needle into the target. Further, a cannula may beinserted into the target as described above. At a later time, such aswhen the control arm or another component of the device recognizes aslack in the tether, the rotationally biased member may be allowed tofurther de-energize, causing additional rotation of one or morecomponents of the insertion mechanism. This rotation may cause, orallow, the needle to be retracted from the target. The needle may befully retracted in a single step or there may be multiple steps ofretraction.

In one embodiment, translation of the activation mechanism may be a partof, or operate, a NIM activation mechanism. The NIM activation mechanismmay include an enabling mechanism as shown in FIGS. 122A-122B. In thisembodiment, translation of the activation mechanism 9614 may be directlyor indirectly coupled to a slide 96602. In a first configuration, theenabling mechanism is configured such that translation of the activationmechanism and slide does not cause activation of the needle insertionmechanism 96200 or sterile fluid pathway connector 96300.

FIGS. 122A-122B illustrate the enabling mechanism configured such thattranslation of the activation mechanism 9614 (See FIG. 110A) and slide96602 causes activation of the needle insertion mechanism 96200.Transformation of the enabling mechanism from the first configuration tothe second configuration may be initiated by, for example, triggering ofan on-body sensor, or by the elapsing of a predetermined amount of timeafter power-on of the device. The transformation of the enablingmechanism from the first to the second configuration may be performed byrotation of the actuator 96101 which may cause a selector member 96604to become aligned with an aspect of the slide 96602. The selector member96604 may include a ramped surface 96604A which is configured to contacta portion of the slide 96602 upon translation of the activationmechanism 14 and slide 96602. The selector member 96604 may be mountedto or be an integral portion of the gear interface such as key 961101.Contact of the slide 96602 with the selector member 96604 may cause theslide 96602 to be displaced such that a portion of the slide is alignedwith a portion of a throw arm or control arm 96606, such as protrusion96606A. In this configuration, translation of the activation mechanism14 causes translation of the throw arm 96606. Translation of the throwarm 96606 causes activation of the needle insertion mechanism 96200 toinsert the fluid path into the target. During manufacturing,transportation, and storage, the enabling mechanism is in the firstconfiguration in which depression of the activation mechanism 9614 doesnot activate the needle insertion mechanism 96200. In this way, theneedle insertion mechanism is prevented from activating prematurely.Contact of the slide 96602 with the selector member 96604 may causesubstantially rigid body displacement of the slide or, alternatively,the contact may cause a deformation of the slide. For example, the slidemay include a deformable (i.e., less rigid) portion which may bedisplaced by the contact.

One example of a NIM activation mechanism is shown in FIGS. 116A-121B.For clarity, a number of components of the drug delivery device arehidden in these figures. The NIM activation mechanism includes: a slide96602, a throw arm 96606, a NIM interlock 96608, and a NIM retainer96610. Initially, as shown in FIGS. 116A-117B, the NIM retainer 96610 ispositioned such that the NIM retainer 96610 is in contact with aprotrusion 96204 of the NIM 96200 such that the protrusion 96204 isprevented from rotating about axis R (see FIG. 118B), thereby preventingactivation of the NIM 96200. In the embodiment shown, the NIM retainer96610 is configured for rotational movement about axis B (see FIG.120B). The NIM retainer 96610 may, for example, be mounted to thehousing 9612 or to the top plate 961530 at the bore 96610A. For example,a pin or shaft may be disposed in bore 96610A around which the NIMretainer 96610 may rotate. The pin or shaft may an integral portion ofthe housing 9612 or top plate 961530 or, alternatively, may be aseparate component. The NIM retainer 96610 is prevented from rotating bycontact between an arm 96610B of the NIM retainer 96610 with the NIMinterlock 96608. The NIM interlock 96608 is disposed for translationalmotion (in the direction of the hatched arrow of FIG. 116B) and isinitially held in position by a flex arm 961530A which may be a portionof the top plate 961530. The NIM interlock 96608 is initially in a firstposition or lock configuration in which it is in contact with oradjacent to a lower surface 96606B of the throw arm 96606.

With the selector member 96604 in the second configuration (shown inFIGS. 122A-122B) depression of the activation mechanism 9614 causestranslation of the throw arm 96606 as described above (in the directionof the solid arrow in FIG. 116A). The ramped surface 96606C of the throwarm 96606 contacts the NIM interlock 96608 and causes the NIM interlock96608 to translate in a direction substantially orthogonal to thedirection of translation of the throw arm 96606. FIGS. 118A-119B showthe position of the throw arm 96606 and NIM interlock 96608 aftertranslation of the throw arm. As shown, in this configuration (e.g., anunlock configuration), the NIM interlock 96608 is positioned adjacent toor in contact with an upper surface 96606D of the throw arm 96606. Thewindow 96608A of the NIM interlock 96608 is aligned with the arm 96610Bof the NIM retainer 96610. Hence, as shown in FIGS. 120A-121B, the NIMretainer 96610 is able to rotate about axis B. The contact surfaces ofprotrusion 96204 and retainer 96610 may be configured such that theprotrusion 96204 applies a rotational force to NIM retainer 96610,thereby causing rotation of NIM retainer 96610 about axis B.Alternatively, or additionally, the NIM retainer 96610 may be biased torotate by a biasing member. The biasing member may be, for example, atorsion spring. Rotation of the NIM retainer 96610 causes the NIMretainer 96610 to disengage the protrusion 96204 of the NIM 96200.Hence, the NIM 96200 is able to activate to insert a fluid path into atarget.

In other embodiments, the NIM interlock 96608 may directly engage aportion of the NIM 96200, such as the protrusion 96204, to initiallyprevent activation of the NIM 96200. Translation of the NIM interlock96608 in the direction orthogonal to the translation of the throw arm96606 may cause the NIM interlock 96608 to disengage the NIM 96200 andallow the NIM 96200 to activate. Also, while the slide 96602 and thethrow arm 96606 are shown here as separate components, it iscontemplated that these can be combined into a single, unifiedcomponent. In such an embodiment, the selector member may initially beconfigured to prevent translation of the slide and/or throw arm.

In another embodiment, the throw arm 96606 is engaged with a portion ofthe NIM whereby translation of the throw arm 96606 allows activation ofthe NIM 96200.

In addition to the advantages described above, the insertion mechanismsdescribed herein may also be capable of terminating flow of medicamentto the target tissue by disconnecting the fluid path. This may be animportant safety feature to protect the target. For example, somemedicaments, such as insulin, can be dangerous, and potentially evendeadly, when administered in too large a quantity and/or at too rapid ofa rate. By providing such automatic safety stop mechanisms, so-called“run-away” delivery of medicament may be prevented, thereby ensuring thesafety of the target. While the methods and associated structures forterminating flow may be discussed with regard to one or more specificinsertion mechanisms disclosed herein, it will be appreciated that themethod and associated structures may be utilized or adapted for any ofthe insertion mechanisms disclosed herein or within the spirit and scopeof this disclosure.

An interruption in delivery of medicament to the target tissue may betriggered, for example, by an error in delivery of the medicament or byan input from the user. For example, the user may realize that they havealready taken their drug dose and wish to pause or terminate drugdelivery from the device. Upon such user input to the device, thedelivery of the drug can be stopped and/or the fluid passageway throughthe needle or cannula may be terminated by retraction of the needle toits fully retracted position.

Additionally or alternatively, the device may pause or terminate drugdelivery if it receives an error alert during operation. For example, ifthe drive mechanism is not functioning correctly, the needle insertionmechanism may be triggered to retract fully and terminate drug deliveryto the target tissue to prevent over-delivery of a medication to thetarget tissue. This capability of the needle insertion mechanismprovides a valuable safety feature for drug delivery to a target.

In some embodiments, retraction is activated upon removal of the drugdelivery device from the target tissue. In other embodiments, retractionis activated if it is determined that an error has occurred in thedelivery of the substances to the target tissue. For example, anocclusion of the drug delivery pathway which prevents the flow ofmedicament may be detected by a sensing function of the drug deliverypump. Upon the sensing of the occlusion an electrical or mechanicalinput may be used to initiate retraction of the needle.

XVIII.C. Fluid Pathway Connector

A number of fluid pathway connectors may be utilized within theembodiments of the present disclosure. Generally, a suitable fluidpathway connector includes a sterile fluid conduit, a piercing member,and a sterile sleeve attached to a drug container or a slidingpierceable seal integrated within a drug container. The fluid pathwayconnector may further include one or more flow restrictors. Upon properactivation of the device 9610, the fluid pathway connector 96300 isenabled to connect the sterile fluid conduit 9630 to the drug containerof the drive mechanism 96100. Such connection may be facilitated by apiercing member, such as a needle, penetrating a pierceable seal of thedrug container of the drive mechanism 96100. The sterility of thisconnection may be maintained by performing the connection within aflexible sterile sleeve. Upon substantially simultaneous activation ofthe insertion mechanism, the fluid pathway between drug container andinsertion mechanism is complete to permit drug delivery into the target.In one such embodiment, the fluid pathway connector may be substantiallysimilar to that described in International Patent Application No.PCT/US2012/054861, published as WO 2015027174 A4 or International PatentApplication No. PCT/US2016/020486 filed Mar. 2, 2016, which are includedby reference herein in its entirety for all purposes. In such anembodiment, a compressible sterile sleeve may be fixedly attachedbetween the cap of the drug container and the connection hub of thefluid pathway connector. The piercing member may reside within thesterile sleeve until a connection between the fluid connection pathwayand the drug container is desired. The sterile sleeve may be sterilizedto ensure the sterility of the piercing member and the fluid pathwayprior to activation.

Alternatively, the fluid pathway connector may be integrated into a drugcontainer as described in International Patent Applications No.PCT/US2013/030478 or No. PCT/US2014/052329, for example, which areincluded by reference herein in their entirety for all purposes.According to such an embodiment, a drug container may have a drugchamber within a barrel between a pierceable seal and a plunger seal. Adrug fluid is contained in the drug chamber. Upon activation of thedevice by the user, a drive mechanism asserts a force on a plunger sealcontained in the drug container. As the plunger seal asserts a force onthe drug fluid and any air/gas gap or bubble, a combination of pneumaticand hydraulic pressure builds by compression of the air/gas and drugfluid and the force is relayed to the sliding pierceable seal. Thepierceable seal is caused to slide towards the cap, causing it to bepierced by the piercing member retained within the integrated sterilefluid pathway connector. Accordingly, the integrated sterile fluidpathway connector is connected (i.e., the fluid pathway is opened) bythe combination pneumatic/hydraulic force of the air/gas and drug fluidwithin the drug chamber created by activation of a drive mechanism. Oncethe integrated sterile fluid pathway connector is connected or opened,drug fluid is permitted to flow from the drug container, through theintegrated sterile fluid pathway connector, sterile fluid conduit, andinsertion mechanism, and into the target for drug delivery. In at leastone embodiment, the fluid flows through only a manifold and a cannulaand/or needle of the insertion mechanism, thereby maintaining thesterility of the fluid pathway before and during drug delivery.

In a preferred embodiment, the sterile fluid pathway connector isinitiated by movement of the needle insertion mechanism, which itself isinitiated by the drive mechanism. Additionally or alternatively, thesterile fluid pathway connector is initiated by movement directly of thedrive mechanism. For example, the drive mechanism may include arotational gear, such as the star gear described in detail herein, thatacts concurrently or sequentially to control the rate of drug delivery,to actuate the needle insertion mechanism, and/or initiate the sterilefluid pathway connector. In one particular embodiment, shown in FIGS.110A-110C, the drive mechanism performs all of these steps substantiallyconcurrently. The drive mechanism rotates a gear that acts upon severalother components. The gear acts on a gear assembly to control the rateof drug delivery, while also contacting a needle insertion mechanism tointroduce a fluid pathway into the target. As the needle insertionmechanism is initiated, the sterile fluid connection is made to permitdrug fluid flow from the drug container, through the fluid conduit, intothe needle insertion mechanism, for delivery into the target as the gearand gear assembly of the drive mechanism control the rate of drugdelivery.

Regardless of the fluid pathway connector utilized by the drug deliverydevice, the drug delivery device is capable of delivering a range ofdrugs with different viscosities and volumes. The drug delivery deviceis capable of delivering a drug at a controlled flow rate (speed) and/orof a specified volume. In one embodiment, the drug delivery process iscontrolled by one or more flow restrictors within the fluid pathwayconnector and/or the sterile fluid conduit. In other embodiments, otherflow rates may be provided by varying the geometry of the fluid flowpath or delivery conduit, varying the speed at which a component of thedrive mechanism advances into the drug container to dispense the drugtherein, or combinations thereof. Still further details about the fluidpathway connector 300 and the sterile fluid conduit 30 are providedhereinafter in later sections in reference to other embodiments.

XVIII.D. Drive Mechanism:

The drive mechanisms of the present disclosure may enable or initiateseveral functions, including: (i) controlling the rate of drug deliveryby metering, providing resistance, or otherwise preventing free axialtranslation of the plunger seal utilized to force a drug substance outof a drug container; (ii) triggering a needle insertion mechanism toprovide a fluid pathway for drug delivery to a target; and (iii)connecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the target. With reference to the embodiments shown in FIGS.111A-111E and 112A-112D, drive mechanism 96100 includes an actuator96101, a gear assembly 96116 including a main gear 96102, a drivehousing 96130, and a drug container 9650 having a cap 9652, a pierceableseal (not visible), a barrel 9658, and a plunger seal 9660. The maingear 96102 may be, for example, a star gear disposed to contact multiplesecondary gears or gear surfaces. A drug chamber 9621, located withinthe barrel 9658 between the pierceable seal and the plunger seal 9660,may contain a drug fluid for delivery through the insertion mechanismand drug delivery device into the target. The seals described herein maybe comprised of a number of materials but are, in a preferredembodiment, comprised of one or more elastomers or rubbers. The drivemechanism 96100 may further contain one or more drive biasing members,one or more release mechanisms, and one or more guides, as are describedfurther herein. The components of the drive mechanism function to forcea fluid from the drug container out through the pierceable seal, orpreferably through the piercing member of the fluid pathway connector,for delivery through the fluid pathway connector, sterile fluid conduit,and insertion mechanism into the target.

In one particular embodiment, the drive mechanism 96100 employs one ormore compression springs as the biasing member(s). Upon activation ofthe drug delivery device by the user, the power and control system maybe actuated to directly or indirectly release the compression spring(s)from an energized state. Upon release, the compression spring(s) maybear against and act upon the plunger seal to force the fluid drug outof the drug container. The compression spring may bear against and actupon a piston which, in turn, acts upon the plunger seal to force thefluid drug out of the drug container. Optionally, as will be describedfurther hereinafter, the piston may include one or more safetymechanisms which may be configured to restrict the translation of thepiston to restrict flow of medicament to the target. Such safetymechanisms can include a brake mechanism, a plunger seal piercingmechanism, and a plunger seal displacing mechanism, such as thosedescribed in detail herein. The fluid pathway connector may be connectedthrough the pierceable seal prior to, concurrently with, or afteractivation of the drive mechanism to permit fluid flow from the drugcontainer, through the fluid pathway connector, sterile fluid conduit,and insertion mechanism, and into the target for drug delivery. In atleast one embodiment, the fluid flows through only a manifold or needleand a cannula of the insertion mechanism, thereby maintaining thesterility of the fluid pathway before and during drug delivery. Suchcomponents and their functions are described in further detail herein.

Referring now to the embodiment of the drive mechanism shown in FIGS.111A-111E and 112A-112D, drive mechanism 96100 includes an actuator96101, a gear assembly 96116 including a main gear 96102, a drivehousing 96130, and a drug container 9650 having a cap 9652, a pierceableseal (not visible), a barrel 9658, and a plunger seal 9660. The maingear 96102 may be, for example, a star gear disposed to contact multiplesecondary gears or gear surfaces. A drug chamber 9621, located withinthe barrel 9658 between the pierceable seal and the plunger seal 9660,may contain a drug fluid for delivery through the insertion mechanismand drug delivery device into the target. Compressed within the drivehousing 96130, between the drug container 9650 and the proximal end ofthe housing 96130, are one or more drive biasing members 96122 and apiston 96110, wherein the drive biasing members 96122 are configured tobear upon an interface surface 96110C of the piston 96110, as describedfurther herein. Optionally, a cover sleeve (not shown) may be utilizedbetween the drive biasing members 96122 and the interface surface 96110Cof the piston 96110 to, for example, promote more even distribution offorce from the drive biasing member 96122 to the piston 96110, preventbuckling of the drive biasing members 96122, and/or hide the biasingmembers 96122 from user view. Interface surface 96110C of piston 96110is caused to rest substantially adjacent to, or in contact with, aproximal end of seal 9660. Although the embodiments shown in FIGS.111A-111E and 112A-112D show a singular biasing member it is alsocontemplated that one or more biasing members disposed to act inparallel or in series may be used.

As best shown in FIG. 111E and FIG. 112D, the piston 96110 may becomprised of one or more components and have an interface surface tocontact the plunger seal. A tether, ribbon, string, or other retentionstrap (referred to herein as the “tether” 96525; See FIG. 112D) may beconnected at one end to the piston 96110. For example, the tether 96525may be connected to the piston 96110 by retention between the twocomponents of the piston 96110 when assembled. FIG. 112D shows thebiasing member partially hidden to allow the connection of the tether tothe piston to be viewed. The tether 96525 is connected at another end toa winch assembly 96520 of a delivery control or regulating mechanism96500. Winch assembly 96520 includes winch gear 96520A and winch drum96520B rotation of which is coupled, for example by a keyedrelationship. Through the use of the winch assembly 96520 connected toone end of the tether 96525, and the tether 96525 connected at anotherend to the piston 96110, the regulating mechanism 96500 functions tocontrol, meter, provide resistance, or otherwise prevent free axialtranslation of the piston 96110 and plunger seal 9660 utilized to forcea drug substance out of a drug container 9650. Accordingly, theregulating mechanism 96500 is a portion of the gear assembly 96116aspect of the drive mechanism, which together function to control therate or profile of drug delivery to the target.

As shown in FIGS. 111A-111E and 112A-112D, and in isolation in FIGS. 113and 114A-114B, in embodiments of the present disclosure, the regulatingmechanism 96500 includes a gear assembly controlled by an actuator 96101of the drive mechanism 96100. The regulating mechanism retards orrestrains the distribution of tether 96525, only allowing it to advanceat a regulated or desired rate or according to selected intervals. Thisrestricts movement of piston 96110 within barrel 9658, which is pushedby one or more biasing members 96122, hence, controlling the movement ofplunger seal 9660 and delivery of the drug contained in chamber 9621. Asthe plunger seal 9660 advances in the drug container 9650, the drugsubstance is dispensed through the sterile pathway connection 96300,conduit 9630, insertion mechanism 96200, and into the target for drugdelivery. The actuator 96101 may be a number of power/motion sourcesincluding, for example, a solenoid, a stepper motor, or a rotationaldrive motor. In a particular embodiment, the actuator 96101 is arotational stepper motor engaged with a gear interface such as a shaftwith a notch that corresponds with the gear teeth of the main/star gear96102. In at least one embodiment, the notch of the gear interface formsa recess within which one or more teeth of the main gear may partiallyreside during operation of the system. This is more clearly visible inFIGS. 114A-114B. When the gear interface 96101A is in alignment with atooth 96102A of the main gear 96102, rotational motion of the motor96101 allows rotation of the main gear 96102. When the notch is betweengear teeth of the main gear, it may act as a resistance for, forexample, rotation, back-spinning or unwinding of the gear assembly96116. In one particular embodiment, the motor 96101 utilizes analternating direction type motor to rotate the motor 96101 backwards andforwards. This configuration aids in the prevention of a runawaycondition, where the motor and the gears are freely permitted to rotate,by using the multi-direction of the motor to prevent continuous spin inone direction (as would be needed for a runaway condition). Further,because main gear 96102 is only able to advance when a tooth 96102A isaligned with the notch of the gear interface 96101A, main gear 96102 isonly able to incrementally rotate. The bi-directional movement of themotor, coupled with the use of the gear interface coupled to the motor,provide suitable safety features to prevent a runaway condition thatcould potentially lead to over-delivery of drug to the target. Furtherdetail about the gear assembly 96116, regulating mechanism 96500, anddrive mechanism 96100 are provided herein. In a particular embodimentshown in FIGS. 114A-114B, the regulating element 96500 further includesone or more gears 96511, 96512, 96513, 96514, of a gear assembly 96516.One or more of the gears 96511, 96512, 96513, 96514 may be, for example,compound gears having a small diameter gear attached at a shared centeraxis to a large diameter gear. Gear 96513 may be rotationally coupled towinch gear 96520A, thereby coupling rotation of gear assembly 96516 towinch assembly 96520. Compound gear 96512 engages the small diametergear 96513 such that rotational movement of the compound gear aspect96512B is conveyed by engagement of the gears (such as by engagement ofcorresponding gear teeth) to gear 96513. Gear aspect 96512A is engagedwith gear aspect 96512B, thereby coupling rotation of compound gear96512 with compound gear 96511. Compound gear aspect 96511A, therotation of which is coupled to gear aspect 96511B, is caused to rotateby action of compound gear aspect 96102B of the main/star gear 96102A.Compound gear aspect 96102B, the rotation of which is coupled tomain/star gear 96102A, is caused to rotate by interaction betweenmain/star gear 96102A and interface 96101A of the actuator 96101. Thus,rotation of main/star gear 96102A is conveyed to winch assembly 96520.Accordingly, rotation of the gear assembly 96516 initiated by theactuator 96101 may be coupled to winch assembly 96520 (i.e., through thegear assembly 96516), thereby controlling the distribution of tether96525, and the rate of movement of plunger seal 9660 within barrel 9658to force a fluid from drug chamber 9621. The rotational movement of thewinch assembly 96520, and thus the axial translation of the piston 96110and plunger seal 9660, are metered, restrained, or otherwise preventedfrom free axial translation by other components of the regulatingelement 96500, as described herein. As described above, the actuator96101 may be a number of known power/motion sources including, forexample, a motor (e.g., a DC motor, AC motor, or stepper motor) or asolenoid (e.g., linear solenoid, rotary solenoid). One of skill in theart will recognize that regulating mechanism 96500 may include anynumber of gears to achieve the desired gear ratio. The regulatingmechanism may provide any desirable gear ratio between main gear 96102Aand winch gear 96520A. The gear ratio may, for example, be selectedbased on the desired drug delivery profile. Additionally, the resolutionof the gear assembly may be configured based on the number of teeth ofmain gear 96102. The more teeth that main gear 96102 has, the finer theresolution of the gear assembly. Conversely, if the main gear 96102 hasfewer teeth the gear assembly will have a coarser resolution (i.e., moredrug fluid will be delivered per each rotation of the actuator).

The embodiment described above and shown in FIGS. 110A-114D show anactuator 96101 that is in vertical alignment and in direct engagementwith gear interface 96101A and, thereby, the main/star gear 96102. Aswould readily be appreciated by one having ordinary skill in themechanical arts, the actuator 96101 could be modified to be inhorizontal alignment. Additionally or alternatively, the actuator 96101could be modified to be in indirect engagement with the gear interface96101A and main/star gear 96102. The embodiments shown in FIGS.115A-115B show an actuator 96101 that is in horizontal alignment andindirect engagement with the gear interface 96101A and main/star gear96102. Such an embodiment may utilize a rack and pinion engagement, adrive screw, or a worm gear 96101W, as shown in FIGS. 115A-96115B, tochange the direction of motion from horizontal to vertical (i.e.,perpendicular interaction). Actuator 96101 rotates worm gear 96101W,which engages gear 96101G and conveys the motion to the gear interface96101A, in this embodiment a shaft with a notch. The gear interface96101A engages main/star gear 96102 to enable operation of the drivemechanism and the drug delivery device, as described herein. Main/stargear 96102 may also drive operation of gear 96112 to enable operation ofthe needle insertion mechanism 96200, as described herein. In oneparticular embodiment, the actuator 96101 utilizes an alternatingdirection type motor to rotate the worm gear 96101W, gear 96101G, andgear interface 96101A backwards and forwards. This configuration aids inthe prevention of a runaway condition, where the motor and the gears arefreely permitted to rotate, by using the multi-direction of the motor toprevent continuous spin in one direction (as would be needed for arunaway condition). This bi-directional movement of the actuator 96101,coupled with the use of the worm gear 96101W, gear 96101G, and gearinterface 96101A with the main/star gear 96102, provide suitable safetyfeatures to prevent a runaway condition that could potentially lead toover-delivery of drug to the target. Additionally, the gear interface96101A may include a stop member 96101B that stops the rotation of thegear interface 96101A against a stop block 150. Stop block 96150 furtherprevents over-rotation of the gear interface 96101A and, accordingly,the main/star gear 96102 to prevent a runaway condition that couldpotentially lead to over-delivery of drug to the target. For the deviceto function in this configuration, the gear interface 96101A must berotated backwards in the other direction before rotating forwards againto progress the main/star gear 96102 because the stop member 96101Bprevents over rotation in one direction by interaction with the stopblock 96150. Additionally, the geometry of worm gear 96101W may beconfigured such that it is self-locking and/or cannot be back-driven bygear 96101G. This may be done by configuration of parameters such as:pitch, lead angle, pressure angle, and number of threads. In so doing,runaway conditions of the drive mechanism will be prevented by the wormgear's resistance to rotations that are not caused by actuator 96101.

In another embodiment, the actuator 96101 is rotationally coupled to agear interface such as a key 961101, such as that shown in FIGS.124A-124B. The actuator may be an alternating direction type motor asdescribed above. The key 961101 may be a shaft with one or more flanges961101A, 961101B, which interface with main gear 961102. The firstflange 961101A and second flange 961101B are offset along the length ofthe shaft. Alternating clockwise and anti-clockwise rotation of the key961101 allows stepwise rotation of the main gear 961102. In theembodiment shown, the key 961101 has two flanges but it is contemplatedthat the key 961101 may include any number of flanges. As shown, the key961101 may further include a rotation limiter 961101C and a statusreader interface 961101D. The second flange 961101B may further includea step 961101E. These features are configured to interact with the maingear 961102 during operation to control rotation of the gear assembly961516 and, optionally, interact with a status reader 961550 to monitorthe rotation of the regulating mechanism 961500. The rotation limiter961101C and status step 961101E are configured such that contact ofthese features with the main gear 961102 restricts continued rotation ofthe key.

As shown in FIG. 125, the main gear 961102 includes variablepass-throughs that allow passage of the flanges 961101A, 961101B of thekey 961101 and, thereby, rotation of the key 961101. As shown, the maingear 961102 may include cyclically alternating large 961102A and small961102B pass-throughs, each separated by a tooth 961102C. The size ofthe pass-throughs may be configured to control rotation of the key961101 to allow operation of the regulating mechanism 961500 to bemonitored, as will be described further hereinafter.

The steps of operation of the key 961101 and main gear 961102 aredescribed further with reference to FIGS. 126A-129B. Although sequentialterms such as first, second, third, and fourth are used to describe thestages of operation, these terms are used for explanatory purposes only.The key and gear train may begin in any of the described configurations.FIGS. 126A-126B show the key 961101 and main gear 961102 in a firstconfiguration. A tooth of the main gear 961102 is contacting the firstflange 961101A of the key 961101 and rotation of the main gear 961102 isthereby restricted. A portion of the first flange 961101A of the key961101 is disposed in a large pass-through 961102A of the main gear961102. The tension applied to the tether by the drive biasing memberapplies a torque to the main gear (through the regulating mechanism961500) that is in the direction of the solid arrow shown in FIG. 126B.The contact between the tooth 961102C of the main gear 961102 and thefirst flange 961101A of the key resists rotation in this direction.

To allow the main gear 961102 to advance, the key 961101 may be rotatedsuch that the first aperture 961101F of the first flange 961101A isaligned with the tooth 961102C of the main gear 961102. In theembodiment shown, the rotation is in the direction of the dashed arrowof FIG. 126B. The amount of rotation of the key 961101 will be limitedby contact of the step 961101E of the second flange 961101B with themain gear 961102. In this position, the key 961101 is not preventingrotation of the main gear 961102 as no teeth of the main gear are incontact with the key. If the regulating mechanism 961500 is operatingproperly, the tension on the tether will cause the main gear 961102 torotate (in the direction of the solid arrow of FIG. 126B) until a tooth961102C of the main gear 961102 comes into contact with the secondflange 961101B of the key 961101. Hence, the main gear 961102 advances acontrolled amount, allowing the rotation of the key 961101 to controlunspooling of the tether and translation of the piston. As shown inFIGS. 127A-127B, in this position, the contact between the step 961101Eof the second flange 961101B and the main gear 961102 restricts rotationof key 961101 and, thereby, prevents the status reader interface 961101Dfrom coming into contact with the status reader 961550.

From this position, the main gear 961102 may be allowed to advanceanother step by rotation of the key 961101 in the opposite direction tothat rotated previously. For example, if the key was rotated in ananti-clockwise direction to transform from the first position to thesecond position, the key would now be rotated in a clockwise directionto transform from the second position to the third position. Afterrotation of the second flange 961101B past the main gear 961102 suchthat the second aperture 961101G is aligned with the main gear 961102,the tooth 961102C of the main gear 961102 that was in contact with thesecond flange 961101B is able to advance until it comes in contact withthe first flange 961101A. This, third position, is shown in FIGS.128A-28B. In this position, the first flange 961101A is disposed in asmall pass-through 961102B of the main gear 961102 and the second flange961101B is aligned with, but not disposed in, a large pass-through961102A of the main gear 961102.

Rotation of the key 961101 will again allow advancement of the main gear961102. In transforming from the third position to the fourth position,however, the step 961101E of the second flange 961101B will not makecontact with the main gear 961102 as the large pass-through 961102A ofthe main gear 961102 is configured to allow passage of the step 961101E(i.e., the large pass-through is large enough to allow the step to passthrough it). Hence, as shown in FIGS. 129A-129B, in the fourth position,the status reader interface 961101D of the key 961101 contacts thestatus reader 961550. This contact causes a signal to be sent to thepower and control system. The status reader may be, for example, adetector switch which creates or modifies an electrical signal uponcontact with, or displacement of, the status reader arm 961550A. Thestatus reader 961550 may be mounted to the housing 9612 or top plate961530 and be in electrical communication with the power and controlsystem.

In this way, the operation of the regulating mechanism may be monitored.In the embodiment described above, when the main gear 961102 isoperating properly, the key 961101 will contact the status reader 961550at a predefined rotation interval during operation, for example onceevery four rotations of the key 961101. However, if the main gear 961102is not rotating properly, the key 961101 will contact the status reader961550 at some other interval or not contact the status reader at all.For example, if the main gear 961102 stops rotating in a position,wherein the second flange 961101B is aligned with a large pass-through961102A of the main gear 961102, the key 961101 will contact the statusreader 961550 every other rotation of the key 961101 (i.e., each timethe key is rotated in the direction of the dashed arrow in FIG. 126B).Alternatively, if the main gear 961102 stops rotating in a positionwherein the second flange 961101B is aligned with a small pass-through961102B of the main gear 961102, the key 961101 will be prevented fromcontacting the status reader 961550. Hence, the power and control systemcan compare the frequency of contact between the key and the statusreader with an expected frequency and determine whether the regulatingmechanism is operating properly.

This may provide safety advantages to the target. For example, if thekey 961101 rotates four times and the power and control system does notreceive a signal from the status reader 961550, the power and controlsystem may terminate delivery of medicament to the target. Similarly, ifthe power and control system receives a signal from the status reader961550 after only two rotations, this would also signal a fault in theregulating mechanism and initiate termination of delivery. The power andcontrol system may terminate delivery by activating one or more actionssuch as retraction of the needle or cannula from the target.

While the embodiment described above is configured such that the key961101 contacts the status reader 961550 once every four rotations,these components may be configured for any frequency of activation by,for example, varying the distribution of large 961102A and small 961102Bpass-throughs in the main gear 961102.

Further, the key 961101 may be configured to provide additionaladvantages in preventing runaway drug delivery scenarios. In theembodiment shown in FIGS. 124A-124B, the key 961101 is configured suchthat the main gear 961102 is only able to rotate one rotationalincrement at a time. At all times, because first aperture 961101F andsecond aperture 961101G are not aligned (i.e., they are offset aroundthe circumference of the shaft), at least one of the first flange961101A and the second flange 961101B is positioned to prevent rotationof the main gear 961102 by being in the path of travel of the teeth961102C of the main gear 961102. Further, in the embodiment shown, theflanges 961101A, 961101B of the key 961101 are oriented substantiallyperpendicular to the path of travel of the teeth 961102C of the maingear. Hence, the force applied to the key by the main gear does notimpart a torque on the key and therefore the key 961101 cannot bebackdriven by the main gear 961102. Hence, rotation of the main gear961102 will be restricted by the key 961101 even when the actuator 96101is not powered to prevent rotation of the key 961101.

The drive mechanism may also be configured to allow unrestrainedunspooling of the tether. FIG. 124C shows an embodiment of a key 962101which would allow such a configuration of the drive mechanism. As shown,aperture 962101F of first flange 962101A is circumferentially alignedwith aperture 962101G of second flange 962101B. Hence, upon rotation ofkey 961101, tooth 961102C of main gear 961102 is aligned with bothapertures. This allows main gear 961102 to rotate freely, without beingrestrained by key 962101. As a result, biasing member 96122 is able toexpand without being restrained by the tether. This results insubstantially all of the contents of the drug container being deliveredat one time, at a rate controlled by the stiffness of the biasing memberand the pneumatic/hydraulic resistance of the system. The versatility ofbeing able to configure the drug delivery device to deliver a metereddrug profile over an extended period as described above or,alternatively, to deliver the drug in a single, relatively short doseprovides a number of advantages. Specifically, it allows the device touse like components across a platform of drug delivery devices, therebyproviding economies of scale in terms of component and assembly prices.

Notably, the regulating mechanisms 96500, 961500 and actuators 96101 ofthe present disclosure do not drive the delivery of fluid substancesfrom the drug chamber 9621. The delivery of fluid substances from thedrug chamber 9621 is caused by the expansion of the biasing member 96122from its initial energized state acting upon the piston 96110 andplunger seal 9660. The regulating mechanisms 96500, 961500 insteadfunction to provide resistance to the free motion of the piston 96110and plunger seal 9660 as they are pushed by the expansion of the biasingmember 96122 from its initial energized state. The regulating mechanism96500, 961500 does not drive the delivery but only controls the deliverymotion. The tether limits or otherwise restrains the motion of thepiston 96110 and plunger seal 9660, but does not apply the force for thedelivery. According to a preferred embodiment, the controlled deliverydrive mechanisms and drug delivery devices of the present disclosureinclude a regulating mechanism indirectly or directly connected to atether metering the axial translation of the piston 96110 and plungerseal 9660, which are being driven to axially translate by the biasingmember 96122. The rate of drug delivery as controlled by the regulatingmechanism may be determined by: selection of the gear ratio of gearassembly 96516; selection of the main/star gear 96102; selection of thediameter of winch drum 96520B; using electromechanical actuator 96101 tocontrol the rate of rotation of the main/star gear 96102, 961102; or anyother method known to one skilled in the art. By using electromechanicalactuator 96101 to control the rate of rotation of the main/star gear96102, 961102 it may be possible to configure a drug delivery device toprovide a variable dose rate (i.e., the rate of drug delivery is variedduring a treatment).

In another embodiment, the power and control system of the drug deliverydevice is configured to receive one or more inputs to meter the releaseof the tether 96525 by the winch assembly 96520 and thereby permit axialtranslation of the piston 96110 by the biasing member 96122 to translatea plunger seal 9660 within a barrel 9658. The one or more inputs may beprovided by the actuation of the activation mechanism, a controlinterface, and/or a remote control mechanism. The power and controlsystem may be configured to receive one or more inputs to adjust therestraint provided by the tether 96525 and winch assembly 96520 on thefree axial translation of the piston 96110 upon which the biasing member96122 bears upon to meet a desired drug delivery rate or profile, tochange the dose volume for delivery to the target, and/or to otherwisestart, stop, or pause operation of the drive mechanism. For example, ifthe power and control system has determined that the pump is notoperating properly, the power and control system may terminate rotationof actuator 96101.

The components of the drive mechanism 96100, upon activation, may beused to drive axial translation in the distal direction of the plungerseal 9660 of the drug container 9650. Optionally, the drive mechanism96100 may include one or more compliance features which enableadditional axial translation of the plunger seal 9660, for example, toensure that substantially the entire drug dose has been delivered to thetarget. For example, the plunger seal 9660, itself, may have somecompressibility permitting a compliance push of drug fluid from the drugcontainer.

The novel controlled delivery drive mechanisms of the present disclosuremay optionally integrate status indication into the drug dose delivery.By use of one or more status triggers and a corresponding status reader,the status of the drive mechanism before, during, and after operationcan be relayed to the power and control system to provide feedback tothe user. Such feedback may be tactile, visual, and/or auditory, asdescribed above, and may be redundant such that more than one signal ortype of feedback is provided to the user during use of the device. Forexample, the user may be provided an initial feedback to identify thatthe system is operational and ready for drug delivery. Upon activation,the system may then provide one or more drug delivery status indicationsto the user. At completion of drug delivery, the drive mechanism anddrug delivery device may provide an end-of-dose indication. As theend-of-dose indication is tied to the piston reaching the end of itsaxial translation, the drive mechanism and drug delivery device providea true end-of-dose indication to the user.

The tether 96525 may have one or more status triggers, such aselectrical contacts, optical markings, or electromechanical pins orrecesses, which are capable of contacting or being recognized by astatus reader. In at least one embodiment, an end-of-dose statusindication may be provided to the user once the status reader contactsor recognizes the final status trigger positioned on the tether 96525that would contact the status reader at the end of axial travel of thepiston 96110 and plunger 9660 within the barrel 9658 of the drugcontainer 9650. The status reader may be, for example, an electricalswitch reader to contact the corresponding electrical contacts, anoptical reader to recognize the corresponding optical markings, or amechanical or electromechanical reader configured to contactcorresponding pins, holes, or similar aspects on the tether. The statustriggers may be positioned along the tether 96525 to be read orrecognized at positions which correspond with the beginning and end ofdrug delivery, as well as at desired increments during drug delivery. Asthe drug delivery device is activated and drug delivery is begun byrelease of the biasing member 96122 and the resulting force applied tothe piston 96110 and plunger seal 9660, the rate or profile of drugdelivery to the target is controlled by the regulating mechanism 96500,gear assembly 96516, and winch assembly 96520 releasing the tether 96525and permitting expansion of the biasing member 96122 and axialtranslation of the piston 96110 and plunger seal 9660. As this occurs,the status triggers of the tether 96525 are contacted or recognized bythe status reader and the status of the drive mechanism before, during,and after operation can be relayed to the power and control system toprovide feedback to the user. Depending on the number of status triggerslocated on the tether 96525, the frequency of the incremental statusindication may be varied as desired. As described above, a range ofstatus readers may be utilized depending on the status triggers utilizedby the system.

In a preferred embodiment, the status reader may apply a tensioningforce to the tether 96525. When the system reaches end-of-dose, thetether 96525 goes slack and the status reader 544 is permitted to rotateabout a fulcrum. This rotation may operate an electrical orelectromechanical switch, for example a switch, signaling slack in thetether 96525 to the power and control system. Additionally, a gear ofgear assembly may act as an encoder along with a sensor. Thesensor/encoder combination is used to provide feedback of gear assemblyrotation, which in turn can be calibrated to the position of piston96110 when there is no slack in the tether 96525. For example, rotationof main gear 96102, 961102 may be configured to be monitored by anoptical sensor. A reflective surface coating may be applied to at leasta portion of the face of main gear 96102, 961102 to improve the accuracyof the optical sensor. Together, the status reader and sensor/encodermay provide positional feedback, end-of-dose signal, and errorindication, such as an occlusion, by observing slack in the tether 96525or another component of the drive mechanism prior to reaching theexpected number of motor rotations as counted by the sensor/encoder.

Referring back to FIGS. 111A-111E and 112A-112D, in addition tocontrolling the rate of drug delivery by metering, providing resistance,or otherwise preventing free axial translation of the plunger sealutilized to force a drug substance out of a drug container (therebydelivering drug substances at variable rates and/or delivery profiles);the drive mechanisms of the present disclosure may concurrently orsequentially perform the steps of: triggering a needle insertionmechanism to provide a fluid pathway for drug delivery to a target; andconnecting a sterile fluid pathway to a drug container to permit fluidflow from the drug container to the needle insertion mechanism fordelivery to the target. In at least one embodiment, as shown in FIGS.111A-111E and 96112A-96112D, initial motion by the actuator 96101 of thedrive mechanism 96100 causes rotation of main/star gear 96102. Main/stargear 96102 is shown as a compound gear with aspects 96102A and 96102B(see FIG. 113). In one manner, main/star gear 96102 conveys motion tothe regulating mechanism 96500 through gear assembly 96516. In anothermanner, main/star gear 96102 conveys motion to the needle insertionmechanism 96200 through gear 96112. As gear 96112 is rotated bymain/star gear 96102, gear 96112 engages the needle insertion mechanism96200 to initiate the fluid pathway connector into the target, asdescribed in detail above. In one particular embodiment, needleinsertion mechanism 96200 is a rotational needle insertion mechanism.Accordingly, gear 96112 is configured to engage a corresponding gearsurface 96208 of the needle insertion mechanism 96200. Rotation of gear96112 causes rotation of needle insertion mechanism 96200 through thegear interaction between gear 96112 of the drive mechanism 96100 andcorresponding gear surface 96208 of the needle insertion mechanism96200. Once suitable rotation of the needle insertion mechanism 96200occurs, for example rotation along axis ‘R’ shown in FIG. 111D, theneedle insertion mechanism may be initiated to create the fluid pathwayconnector into the target, as described in detail above.

In an alternative embodiment, as shown in FIGS. 115A-115B, gear 96112may indirectly engage the needle insertion mechanism 96200 to initiatethe fluid pathway connector into the target. For example, gear 96112 maybe configured to engage a corresponding gear surface of a control arm96202 (visible in FIGS. 115A and 6B) that contacts or blocks the needleinsertion mechanism 96200. Rotation of gear 96112 causes movement of thecontrol arm 96202, which may initiate or permit rotation of needleinsertion mechanism 96200. Such a needle insertion mechanism, as shownin FIGS. 115A-115B, includes a rotationally biased member 96210 which isinitially held in an energized state. The rotational biasing member maybe prevented from de-energizing by contact of a component of theinsertion mechanism with a rotation prevention feature, such as ablocking aspect 96206, of the drug delivery device. Rotation ortranslation of blocking aspect 96206 is initially prevented by contactwith control arm 96202. Translation of control arm 96202, caused byrotation of gear 96112, positions control arm 96202 such that it nolonger prevents rotation of blocking aspect 96206. Upon activation ofthe device, or another input, the rotationally biased member 96210 ispermitted to, at least partially, de-energize. This causes one or morecomponents of the insertion mechanism to rotate and, in turn, cause, orallow, the insertion of the needle into the target. Further, a cannulamay be inserted into the target as described above. At a later time,such as when the control arm or another component of the devicerecognizes a slack in the tether 96525, the rotationally biased membermay be allowed to further de-energize, such as by further interactionwith the control arm, causing additional rotation of one or morecomponents of the insertion mechanism. This rotation may cause, orallow, the needle to be retracted from the target. The needle may befully retracted in a single step or there may be multiple steps ofretraction.

As shown in FIGS. 111A-111E and 112A-112D, rotation of the needleinsertion mechanism 96200 in this manner may also cause a connection ofa sterile fluid pathway to a drug container to permit fluid flow fromthe drug container to the needle insertion mechanism for delivery to thetarget. Ramp aspect 96222 of needle insertion mechanism 96200 is causedto bear upon a movable connection hub 96322 of the sterile fluid pathwayconnector 96300. As the needle insertion mechanism 96200 is rotated bythe drive mechanism 96100, ramp aspect 96222 of needle insertionmechanism 96200 bears upon and translates movable connection hub 96322of the sterile fluid pathway connector 96300 to facilitate a fluidconnection therein. Such translation may occur, for example, in thedirection of the hollow arrow along axis ‘C’ shown in FIG. 111B. In atleast one embodiment, the needle insertion mechanism 96200 may beconfigured such that a particular degree of rotation upon rotationalaxis ‘R’ (shown in FIG. 111D) enables the needle/trocar to retract asdetailed above. Additionally or alternatively, such needle/trocarretraction may be configured to occur upon a user-activity or uponmovement or function of another component of the drug delivery device.In at least one embodiment, needle/trocar retraction may be configuredto occur upon end-of-drug-delivery, as triggered by, for example, theregulating mechanism 96500 and/or one or more of the status readers asdescribed above. During these stages of operation, delivery of fluidsubstances from the drug chamber 9621 may be initiated, on-going, and/orcompleted by the expansion of the biasing member 96122 from its initialenergized state acting upon the piston 96110 and plunger seal 9660. Asdescribed above, the regulating mechanism 96500 functions to provideresistance to the free motion of the piston 96110 and plunger seal 9660as they are pushed by the expansion of the biasing member 96122 from itsinitial energized state. The regulating mechanism 96500 does not drivethe delivery but only controls the delivery motion. The tether limits orotherwise restrains the motion of the piston 96110 and plunger seal9660, but does not apply the force for the delivery. This is visiblethrough the progression of the components shown in FIGS. 111A-111E and112A-112D. The motion of the piston 96110 and plunger seal 9660 as theyare pushed by the expansion of the biasing member 96122 from its initialenergized state are shown in the direction of the solid arrow (FIG. 2D)along axis ‘A’ from proximal or first position ‘P’ to the distal orsecond position ‘D’, as shown in the transition of FIGS. 111A-111E and112A-112D.

Further aspects of the novel drive mechanism will be described withreference to FIG. 113 and FIGS. 114A-114B. FIG. 113 shows a perspectiveview of the drive mechanism, according to at least a first embodiment,during its initial locked stage. Initially, the tether 96525 may retainthe biasing member 96122 in an initial energized position within piston96110. Directly or indirectly upon activation of the device by the user,the drive mechanism 96100 may be activated to permit the biasing memberto impart a force to piston 96110 and therefore to tether 96525. Thisforce on tether 96525 imparts a torque on winch drum 96520B which causesthe gear assembly 96516 and regulating mechanism 96500 to begin motion.As shown in FIG. 114A, the piston 96110 and biasing member 96122 areboth initially in a compressed, energized state behind the plunger seal9660. The biasing member 96122 may be maintained in this state untilactivation of the device between internal features of drive housing96130 and interface surface 96110C of piston 96110. As the drug deliverydevice 9610 is activated and the drive mechanism 96100 is triggered tooperate, biasing member 96122 is permitted to expand (i.e., decompress)axially in the distal direction (i.e., in the direction of the solidarrow shown in FIG. 96111D). Such expansion causes the biasing member96122 to act upon and distally translate interface surface 96110C andpiston 96110, thereby distally translating plunger seal 9660 to pushdrug fluid out of the drug chamber 9621 of barrel 9658. In at least oneembodiment, an end-of-dose status indication may be provided to the useronce the status reader contacts or recognizes a status triggerpositioned on the tether 96525 to substantially correspond with the endof axial travel of the piston 96110 and plunger seal 9660 within thebarrel 9658 of the drug container 9650. The status triggers may bepositioned along the tether 96525 at various increments, such asincrements which correspond to certain volume measurement, to provideincremental status indication to the user. In at least one embodiment,the status reader is an optical status reader configured to recognizethe corresponding optical status triggers on the tether. As would beunderstood by an ordinarily skilled artisan, such optical statustriggers may be markings which are recognizable by the optical statusreader. In another embodiment, the status reader is a mechanical orelectromechanical reader configured to physically contact correspondingpins, holes, or similar aspects on the tether. Electrical contacts couldsimilarly be utilized on the tether as status indicators which contactor are otherwise recognized by the corresponding electrical statusreader. The status triggers may be positioned along the tether 96525 tobe read or recognized at positions which correspond with the beginningand end of drug delivery, as well as at desired increments during drugdelivery. As shown, tether 96525 passes substantially axially throughthe drive mechanism housing 96130, the biasing member 96122, andconnects to the piston 96110 to restrict the axial translation of thepiston and the plunger seal 9660 that resides adjacent thereto.

The novel embodiments of the present disclosure may be utilized tometer, restrain, or otherwise prevent free rotational movement of winchdrum 96520B and, thus, axial translation of the components of thecontrolled delivery drive mechanism 96100. Accordingly, the regulatingmechanism 96500 only controls the motion of the drive mechanism, butdoes not apply the force for the drug delivery. One or more additionalbiasing members 96122, such as compression springs, may be utilized todrive or assist the driving of the piston 96110. For example, acompression spring may be utilized within the drive housing 96130 forthis purpose. The regulating mechanism 96500 only controls, meters, orregulates such action. The controlled delivery drive mechanisms and/ordrug delivery devices of the present disclosure may additionally enablea compliance push to ensure that substantially all of the drug substancehas been pushed out of the drug chamber 9621. The plunger seal 9660,itself, may have some compressibility permitting a compliance push ofdrug fluid from the drug container. For example, when a pop-out plungerseal is employed, i.e., a plunger seal that is deformable from aninitial state, the plunger seal may be caused to deform or “pop-out” toprovide a compliance push of drug fluid from the drug container.Additionally or alternatively, an electromechanical status switch andinterconnect assembly may be utilized to contact, connect, or otherwiseenable a transmission to the power and control system to signalend-of-dose to the user. This configuration further enables trueend-of-dose indication to the user.

In at least one embodiment, incremental status indication may beprovided to the user by reading or recognizing the rotational movementof one or more gears of gear assembly 96516. As the gear assembly 96516rotates, a status reader may read or recognize one or more correspondingstatus triggers on one of the gears in the gear assembly to provideincremental status indication before, during, and after operation of thevariable rate controlled delivery drive mechanism. A number of statusreaders may be utilized within the embodiments of the presentdisclosure. For example, the drive mechanism may utilize a mechanicalstatus reader which is physically contacted by gear teeth of one of thegears of the gear assembly. As the status reader is contacted by thestatus trigger(s), which in this exemplary embodiment may be the gearteeth of one of the gears (or holes, pins, ridges, markings, electricalcontacts, or the like, upon the gear), the status reader measures therotational position of the gear and transmits a signal to the power andcontrol system for status indication to the user. Additionally oralternatively, the drive mechanism may utilize an optical status reader.The optical status reader may be, for example, a light beam that iscapable of recognizing a motion and transmitting a signal to the powerand control system. For example, the drive mechanism may utilize anoptical status reader that is configured to recognize motion of the gearteeth of one of the gears in the gear assembly (or holes, pins, ridges,markings, electrical contacts, or the like, upon the gear). Similarly,the status reader may be an electrical switch configured to recognizeelectrical contacts on the gear. In any of these embodiments, the sensormay be utilized to then relay a signal to the power and control systemto provide feedback to the user.

As would be appreciated by one having ordinary skill in the art, opticalstatus readers and corresponding triggers, electromechanical statusreaders and corresponding triggers, and/or mechanical status readers andcorresponding triggers may all be utilized by the embodiments of thepresent disclosure to provide incremental status indication to the user.While the drive mechanisms of the present disclosure are described withreference to the gear assembly and regulating mechanism shown in thefigures, a range of configurations may be acceptable and capable ofbeing employed within the embodiments of the present disclosure, aswould readily be appreciated by an ordinarily skilled artisan.Accordingly, the embodiments of the present disclosure are not limitedto the specific gear assembly and regulating mechanism described herein,which is provided as an exemplary embodiment of such mechanisms foremployment within the controlled delivery drive mechanisms and drugdelivery pumps.

In at least one embodiment of the present disclosure, the deliveryprofile of the medicament is adjustable. For example, it may bedesirable to deliver a bolus injection of medicament before, during, orsubsequent to certain activities such as eating, exercising, sleeping,etc. A “bolus injection” is any measured drug volume that is deliveredoften irrespective of the delivery time or duration. Conversely, a“basal injection” is often a controlled rate of delivery and/or a drugdelivery profile having various rates of delivery at different timeintervals. Similarly, the user may desire to increase or decrease thebasal delivery rate of the medicament at these or other times. In atleast one embodiment, the delivery profile may be adjustable by the userto achieve this desired drug delivery. The user may adjust the deliveryprofile by interacting with the drug delivery device itself or,alternatively, may use an external device, such as a smart-phone, to doso. For example, the user may adjust the delivery profile by displacingthe activation mechanism or may engage a separate device-integrated orexternal delivery control mechanism.

In another embodiment of the present disclosure, the delivery profilemay be adjusted automatically based on one or more inputs. For example,the delivery profile may be adjusted based on activity level, heartrate, blood sugar level, blood pressure, etc. As above, thesemeasurements may be used to determine the need for a bolus injection orfor the increase or decrease of the basal injection delivery rate oradjustment to the basal injection delivery profile. In at least oneembodiment, these input measurements may be monitored by the deviceitself. Additionally, or alternatively, they may be monitored by asecondary device such as a smart-phone, smart watch, heart rate monitor,glucose monitor, blood pressure monitor, or the like. In someembodiments, the delivery profile may be adjusted based on thesemeasurements with no required user intervention. In the case ofmonitoring and/or control by a secondary device, the secondary deviceand drug delivery device may be in wireless or wired communication withone another. This communication may be through Bluetooth, near fieldcommunication, Wi-Fi, or any other method known to one having ordinaryskill in the relevant art of device interconnectivity.

In a preferred embodiment, however, the monitoring/adjustment mechanismmay alert and make recommendations to the user and the user may haveactive control to initiate/authorize or disregard the recommendationmade by the monitoring/adjustment mechanism. For example, if one or moreof the measurements is above or below a specified threshold value thedevice may emit an audible, visual, or tactile alert to the user. In oneexample, the alert is provided by a vibration of the device, therebyproviding a discrete alert to the user. Additionally or alternatively,the alert may be provided by the user's smart-phone or other secondarydevice. The user may be able to view the current status of themeasurements in a computer program or web interface on the deviceitself, a computer, smart-phone, or other device. The computer programor web interface may provide a recommended adjustment to the deliveryprofile. Based on this information, the user may adjust the deliveryrate of the drug delivery device. As above, the user may adjust thedelivery profile by displacing the activation mechanism or engaging aseparate device-integrated or external delivery control mechanism.

In one embodiment, in response to a signal to adjust the deliveryprofile, either based on user input or based on the measurementsdescribed above, the power and control system may cause a change in therate of movement of actuator 96101. The change in the rate of movementof actuator 96101 causes a change in the rotation rate of regulatingmechanism 96500, 961500 which, in turn, controls the rate of drugdelivery to the target. Alternatively, the delivery profile may bealtered by a change in the characteristics of the flow path ofmedicament through the conduit connecting the drug container andinsertion mechanism. The change may be caused by the introduction,removal, or modification of a flow restrictor which restricts flow ofmedicament from the drug container to the insertion mechanism. Forexample, a flow restrictor may have multiple flow paths which may beselectively placed in fluid communication with an input and an output ofthe flow restrictor. By providing flow paths which are of differentlength or cross-section the rate of delivery may be controlled. In otherembodiments, the delivery profile may be altered by the introduction orremoval of an impingement of the conduit. An impingement of the flowpath may interrupt or slow flow of medicament through the conduit,thereby controlling the rate of delivery to the target. Accordingly, oneor more embodiments of the present disclosure are capable of producing achange to the rate of medicament delivery from the drug containerthereby providing a dynamic control capability to the drive mechanismand/or the drug delivery device.

In order to quickly prime the drug delivery device, while conservingenergy, the drug delivery device may include a priming mechanism such asthat shown in FIGS. 130A-113. Priming mechanism 96700 may allowunwinding of the tether and displacement of the piston without rotationof actuator 96101. This displacement of piston 96110 may provide atleast two benefits. First, any gap that is present between piston 96110and plunger seal 9660 after assembly will be quickly closed, bringingthe two into contact such that they are ready to begin delivery of themedicament. Second, after piston 96110 is brought into contact withplunger seal 9660, continued translation of piston 96110 will causecommensurate displacement of plunger seal 9660. This may allow theprimable drug delivery device containing the priming mechanism to beprimed. Upon activation of the fluid pathway connector and the openingof the fluid path from the drug container, translation of plunger seal9660 may cause air or gas that is initially present in fluid pathwayconnector 96300, fluid conduit 9630, and needle insertion mechanism96200 to be expelled. This air or gas may be replaced by the medicamentcontained in the drug container to allow for delivery of the medicamentto the target tissue to begin.

In the embodiment shown in FIGS. 130A-133, the priming mechanismincludes winch gear 961520 and winch drum 961522. The winch drum 961522includes coupler 96702, capstan 96704, and winder 96706. Winch gear961520 is rotationally coupled to the gear interface through the gearassembly. Tether 961525 is wound around capstan 96704 and is engagedwith winder 79606. As a result, tension applied to the tether, by thepiston, results in a torque being applied to capstan 96704. Capstan96704 is keyed to coupler 96702 such that rotation of capstan 96704 istransferred to coupler 96702. In the embodiment illustrated, externalkey aspect 96704A of capstan 96704 is engaged with internal key aspect96702A of coupler 96702 to transfer rotation from one component toanother. In one embodiment, the key aspects are in the form ofcomplementary teeth. Hence, application of a force to tether 961525causes a rotational force to be applied to coupler 96702 in thedirection of the arrow in FIG. 130A.

Winch gear 961520 includes a gear interface such as the spur gearinterface 961520A shown in FIG. 131 which is engaged, through gearassembly 96116 with actuator 96101. Winch gear 961520 further includeshollow 961520E within which coupler 96702 is at least partiallydisposed. Hollow 961520E is configured with features for controlling therotation of coupler 96702, such as ramp 961520D and stop 961520C.Coupler 96702, shown in FIG. 132, includes one or more extensions 96702Bwhich are configured to be relatively flexible. As shown in FIG. 130A,coupler 96702 is initially positioned such that angled face 96702C ofextension 96702B is adjacent to, or in contact with ramp 961520D ofwinch gear 961520. Contact between angled face 96702C and ramp 961520Dprevents inadvertent rotation of coupler 96702 with respect to winchgear 961520.

One or more components of drug delivery device 9610 form a releasemechanism which is initially engaged with release aspect 96702D ofcoupler 96702. This engagement initially prevents rotation of coupler96702. The release mechanism may be caused to release rotation ofcoupler 96702 by an action of the user, such as depression of activationmechanism 9614. Alternatively, the rotation mechanism may be caused toallow rotation of coupler 96702 by an action of power and control system96400. Upon disengagement of the release mechanism, and in response to atorque applied by tether 96525, coupler 96702 rotates to the positionshown in FIG. 130B. In this position, extension 96702B is in contactwith stop 961520C. This contact prevents further relative rotation ofcoupler 96702 with respect to winch gear 961520 in the direction of thearrow in FIG. 130A. Additionally, extension 96702B may engage step961520F of winch gear 961520 to thereby lock coupler 96702 in positionwith respect to winch gear 961520. With coupler 96702 and winch gear961520 in the configuration shown in FIG. 130B, any further rotation ofcoupler 96702 must be accompanied by commensurate rotation of winch gear961520. Because winch gear 961520 is engaged with actuator 96101 throughgear assembly 96116, rotation of coupler 96702 is also controlled byactuator 96101. In this way, the rate of translation of piston 96110 andthe rate of delivery of medicament can be controlled by actuator 96101.Also, the initial translation of piston 96110 and rotation of coupler96702, from the position shown in FIG. 130A to that shown in FIG. 130B,allows assembly tolerances to be taken up and the primable drug deliverydevice to be primed without rotation of the actuator. This allows theprimable drug delivery device to conserve energy during this initialstage of operation.

In at least one embodiment, the drug delivery device and or drivemechanism include one or more safety mechanisms for automaticallyslowing or terminating the flow of medicament to the target in the eventof a fault in delivery. This may be a beneficial feature in the deliveryof controlled substances. Some substances, such as insulin, can beharmful or even deadly if delivered in too large a quantity or at toorapid of a delivery rate. The safety mechanisms described herein may beused to ensure that a so-called “run-away” delivery does not occur. Forexample, means may exist for terminating or restraining the flow of themedicament in the case of slack in, or failure of, the tether duringoperation.

In one embodiment, the safety mechanism is a brake mechanism as shown inFIGS. 141A-141B. Disposed within barrel 9658 are brake 9664, sleeve9662, and plug 9668, and optionally retainer 9666. Biasing member 96122bears against sleeve 9662. Tether 96525 is engaged with plug 9668,thereby allowing tether 96525 to restrain the motion of sleeve 9662.This restraint controls the rate of expansion or de-energizing ofbiasing member 96122. When tether 96525 is under tension, plug 9668bears against distal face 9664A of brake 9664, causing proximal face9664B of brake 9664 to bear against sleeve 9662. Due to this contact,and the profile of the distal end 9662A of sleeve 9662, brake 9664 ismaintained in a substantially conical configuration as shown in FIG.141A. In this configuration, expansion or de-energizing of biasingmember 96122 is restrained by the tether. Also, in this conicalconfiguration, the outer diameter of brake 9664 is less than the innerdiameter of barrel 9658, thus translation of the brake is not restrainedby contact with the inner wall of the drug container. This permits thebrake to be in a position that is not sufficient for braking contactwith the inner wall of the barrel. Braking contact is contact sufficientto restrain or prevent further de-energizing of the biasing member anddoes not necessarily require complete contact of the brake with theinner wall of the barrel. Similarly, the brake may be retained in aninitial state not in braking contact with the inner wall of the barrel,but does not necessarily require no contact with the inner wall of thebarrel. In at least one embodiment, some contact between the brake andthe inner wall of the barrel may be desired prior to activation of thebrake mechanism, for example to center the brake within the barrel, aslong as the brake does not substantially restrain or prevent furtherde-energizing of the biasing member prior to activation of the brakemechanism. Also, a portion of brake 9664 is in contact with retainer9666. Because brake 9664 is maintained in this configuration by plug9668 and sleeve 9662, translation of sleeve 9662, caused bydecompression of biasing member 96122, is transferred to retainer 9666.Likewise, contact of retainer 9666 with plunger seal 9660 causestranslation of plunger seal 9660.

As shown in FIG. 141B, in the event of slack in, or failure of, tether96525, plug 9668 is no longer held in position by tether 59625 and,therefore, no longer restrains motion of sleeve 9662. As biasing member96122 decompresses or de-energizes, brake 9664 transforms to arelatively less conical or flatter configuration. This may be caused bya natural bias of brake 9664 to transform to this configuration or,alternatively, may be caused by contact of brake 9664 with both retainer9666 and sleeve 9662. As the brake is transformed, it comes into contactwith the inner wall of barrel 9658. The brake thus acts as a wedge torestrict translation of sleeve 9662. This may prevent furthertranslation or may act to restrict the rate of translation. Optionally,restoring tension in the tether may cause the plug to contact the brakeand to transform the brake back to its conical configuration and thusrestore normal operation of the drug delivery device.

FIGS. 141A-141B show the plug as having a spherical shape and the brakeas having a conical shape. Such shapes are used herein merely forexemplary purposes and other shapes or configurations could readily beutilized to achieve the same or similar functionality. For example, theplug may itself be conical in shape and, in one embodiment, be shaped tointerface with the brake when the brake is in a conical shape. In such aconfiguration, the conical shape of the plug assists in maintaining theconical shape of the brake, thereby preventing contact between the outerdiameter of the brake with the inner diameter of the barrel in order torestrict the axial translation of the sleeve 9662 (i.e., applying abraking force). In another embodiment, the brake 9664 could employ astar-shaped or other configuration when in a substantially flattenedposition so as to make contact with the inner diameter of the barrel9658 to prevent or restrict further axial translation of sleeve 9662.Without further translation of sleeve 9662, biasing member 96122 cannotexpand or de-energize further which, in turn, prevents or restrictsfurther drug delivery to the target. This provides a necessary anduseful safety measure for drug delivery, to prevent over-delivery oraccelerated delivery of drug to the target.

In another embodiment, shown in FIGS. 134A-136B, the safety mechanismmay be a plunger seal piercing mechanism 961000 and be positioned atleast partially within the barrel 9658 or the drive housing 961130. Theplunger seal piercing mechanism 961000 may include one or more safetypiercing members 961072, a hub 961074, a piston 961110, and a safetybiasing member 961078. The piston may additionally have an aperture961110A through which the tether 961525 may pass and an internal chamber961110B wherein one or more components of the plunger seal piercingmechanism 961000 may be disposed. The piston may additionally be engagedwith a safety base 961076. The base 961076 may include a centralaperture 961076A through which the tether 961525 may pass and one ormore peripheral apertures 961076B in which the one or more piercingmembers 961072 may be disposed. The one or more safety piercing members961072 may be, for example, a hollow needle, such as a stainless steelneedle. Alternatively, the piercing members 961072 may be solid trocars.They may also be constructed of any other material such as athermoplastic or thermosetting polymer. The one or more piercing members961072 may have a beveled end to increase the efficacy of piercing theplunger seal 961060 and have a lumen 961072B through which material maypass. The one or more piercing members 961072 may be connected to thehub 961074 by any means known to one skilled in the art such as staking,press-fit, and adhesive. Alternatively, the piercing members may beintegrally formed portions of the hub. A proximal plug 961070 and adistal plug 961068 may be fixedly engaged with the tether 961525 suchthat the plugs are fixed in position along the length of the tether961525. The plugs 961068, 961070 may be, for example, ball cablefittings. Alternatively, they may be an integral feature of the tether961525. The plunger seal 961060 may include a cavity 961060A withinwhich the distal end 961072A of the one or more piercing members 961072are initially disposed.

In an initial configuration, as shown in FIGS. 134A-134B, the safetybiasing member 961078 is held in a compressed or energized state betweena portion of hub 961074 such as shoulder 961074A and an internal face961110C of the piston 961110 by tension in the tether 961525. In theembodiment shown, tension of the tether 961525 restricts motion of thehub 961074 by way of the proximal plug 961070 disposed in a cavity961074B of the hub 961074. The stiffness of the safety biasing member961078 is such that during normal operation the tension in the tether961525 is sufficient to prevent decompression of the safety biasingmember 961078. Hence, during normal operation, the hub 961074 and theone or more piercing members 961072 do not translate with respect to thepiston 961110. In the absence of a failure or fault of the drivemechanism tension will be sustained in the tether 961525 and the safetybiasing member 961078 will be prevented from decompressing throughoutthe drug delivery process. The distal plug 961068 may be positioneddistal to at least a portion of the safety mechanism base 961076. Hence,the tension of the tether 961525 is transmitted to the plunger sealpiercing mechanism 961000 by both the distal 961068 and proximal 961070plugs. The piston 961110 may include a flange 961110D disposed betweenthe plunger seal 961060 and the drive biasing member 96122.Alternatively, the drive biasing member 96122 may act on the safetymechanism base 961076. Motion of the drive biasing member 96122 istransmitted through the flange 961110D of the piston 961110 and/or thesafety mechanism base 961076 to the plunger seal 961060. This alsoallows decompression of the drive biasing member 96122 and translationof the plunger seal 961060 to be restricted by the tether 961525. FIGS.135A-135B show the drive biasing member 96122 in a partiallydecompressed state in which the plunger seal 961060 has translateddistally within the barrel 9658.

In the event of failure of the drive mechanism or regulating mechanism,and a resulting reduction in tension in the tether, the safety biasingmember 961078 is able to decompress or de-energize. As shown in FIGS.136A-136B, this decompression of the safety biasing member 961078 causesthe hub 961074 and the one or more piercing members 961072 to translatein the distal direction with respect to the piston 961110. As a result,the distal end 961072A of the one or more piercing members 961072pierces the plunger seal 961060. Upon piercing of the plunger seal961060, a fluid pathway is created from the drug chamber 9621, throughor around the one or more piercing members 961072, and into the piston961110, proximal portion of the barrel 9658, or another aspect of thedrug delivery device 9610. Because the fluid pathway through or aroundthe one or more piercing members 961072 has a lower pressure (i.e., is afluid path of lower resistance) than the fluid pathway through thesterile fluid pathway connector 96300, continued translation of theplunger seal 961060 toward the distal end of the barrel 9658 will resultin the fluid drug traveling through or around the one or more piercingmembers 961072. Thus, the volume of drug delivered through the sterilefluid pathway connector 96300 and delivered to the target will bereduced or terminated. In this way, the safety mechanism 961000 mayreduce or eliminate the risk of a runaway fluid delivery scenario,thereby increasing the safety of the device.

As noted above, the tether 961525 may directly or indirectly restricttranslation of the piston 961110 at one or more locations. For example,in the embodiment shown in FIGS. 134A-136B, the tether 961525 mayrestrict translation of the piston 961110 at the distal plug 961068 andproximal plug 961070 wherein the distal 961068 and proximal 961070 plugsare separated by an intermediate portion 961525A of the tether 961525.This may provide additional, redundant safety mechanisms. For example,if a failure occurs at the distal plug 961068 or in the intermediateportion 961525A of the tether 961525, the rate of decompression of thedrive biasing member 96122 will continue to be restricted due toengagement of the tether 961525 with the piston 961110 at the proximalplug 961070. Failure of the drive mechanism or tether 961525 proximal tothe proximal plug 961070 will result in decompression of the safetybiasing member 961078, piercing of the plunger seal 961060 by the one ormore piercing members 961072, and a restriction or reduction in flow ofdrug fluid to the target as described above. The intermediate portion961525A may be an integral portion of the tether 961525 or may be aseparate component that is directly or indirectly coupled to the tether961525.

During normal operation, the components of the plunger seal piercingmechanism 961000 do not come in contact with the drug. Additionally, inthe event of activation of the plunger seal piercing mechanism 961000,the fluid that passes through or around the one or more piercing members961072 will not be delivered to the target. Therefore, components of theplunger seal piercing mechanism 961000 do not require sterilizationalthough they may be configured for sterilization if desired.

A method of manufacture of a plunger seal piercing mechanism includesone or more of the steps of: passing a tether 961525 through an aperture961110A of a piston 961110; affixing one or more piercing members 961072to a hub 961074; positioning a safety biasing member 961078 against aninternal proximal face 961110C of the piston 961110; passing the tether961525 through an aperture 961074B of the hub 196074; securing aproximal plug 961070 to the tether 961525; passing the tether 961525through a central aperture 961076A of the safety base 961076; securing adistal plug 961068 to the tether 961525.

In another embodiment, shown in FIGS. 137A-137B, the safety mechanism isa plunger seal displacing mechanism 962000. The displacing mechanismincludes piston 962110, spring retainer 962074, sleeve 962084, safetybiasing member 962078, plug 962068, and one or more transfer elements962082. The plug 962068 may be fixedly engaged with the tether 962525.Further, plug 962068 may be positioned distal with respect to at least aportion of the sleeve 962084 such that the plug 962068 restricts distaldisplacement of the sleeve 962084. For example, plug 962068 may bedisposed in recess 962084B of sleeve 962084 (shown in FIG. 140). Thesafety biasing member 962078 is positioned between the piston 962110 andthe sleeve 962084 and is initially prevented from decompressing and/orde-energizing due to the restriction of displacement of the sleeve962084. In an initial position, the transfer elements 962082 aredisposed within apertures 962110A of the piston and are retained in thatposition by contact with the sleeve 962084. The transfer elements 962082are also in contact with a portion of the spring retainer 962074—such asthe contact surface 962074A—and, thereby, prevent translation of thespring retainer 962074 relative to the piston 962110. Hence, the forceimparted on the spring retainer 962074 by the drive biasing member 122is transferred through the transfer elements 962082 to the piston 962110and from the piston 962110 to the plunger seal 962060. The contactsurface 2074A of the spring retainer 962074 may be angled such that itapplies a force to the transfer elements 2082 that is at least partiallyin an inward, radial direction.

Upon failure or fault of the drive mechanism or the tether, the safetybiasing member 962078 will no longer be restricted from decompressing bytension in the tether. The decompression of the safety biasing member962078 causes the sleeve 962084 to translate in the distal directionwith respect to the piston 962110. As the sleeve 962084 translates, thereceiving slot 962084A of the sleeve 962084 becomes aligned with thetransfer elements 962082. When so aligned, the force applied to thetransfer elements 962082 by the spring retainer 962074 causes thetransfer elements 962082 to drop into the receiving slot 962084A. Inthis position, the transfer elements 962082 no longer prevent axial,distal translation of the spring retainer 962074 with respect to thepiston 962110. Because of this, and in response to continueddecompression of the drive biasing member 96122, the spring retainer962074 translates distally with respect to the piston 962110, allowingthe prongs 962074B of the spring retainer 962074 to contact the plungerseal 2060.

The spring retainer 962074 may include any number of prongs 962074B andpreferably includes two or three prongs. The prongs 962074B may beequally spaced around the circumference of the spring retainer 962074or, alternatively, may be unequally spaced. As shown in FIGS. 138-139,the prongs 962074B may include a ramped surface. Contact of the rampedsurface with the plunger seal 962060 may cause inwardly radialdisplacement of the plunger seal 962060. This displacement of theplunger seal 962060 may cause at least a partial loss of contact withthe barrel 9658, allowing the contents of the barrel to flow past theseal 962060 and into the proximal portion of the barrel 9658. Continueddistal translation of the plunger seal 962060 will result in thecontents of the barrel flowing past the seal due to this being a flowpath of lesser resistance than the flow path through the sterile fluidpathway connector 96300. The prongs 962074B of the spring retainer962074 may include bypass features 962074C such as slots or scallopsthat facilitate the flow of fluid past the plunger seal 962060.

In another embodiment, the spring retainer 962074 is configured to causethe plunger seal 962060 to skew within the barrel upon contact (i.e.,cause the central axis of the plunger seal to not be parallel to thecentral axis of the barrel). This allows the contents of the barrel 9658to flow past the plunger seal 962060 and restricts or eliminates furtherdelivery to the target. To cause the skewing of the plunger seal 962060,the spring retainer 962074 may be configured such that it appliespressure to the plunger seal 962060 unevenly such as, for example, byonly having a single prong 962074B.

Other forms of safety mechanisms may be used to ensure that the contentsof the drug container are not delivered at too high a rate. For example,the fluid pathway connector may include a pressure relief or “blowoff”valve which opens in response to increased pressure within the fluidpathway. This increased pressure may be caused by the plunger sealdistally translating at too rapid of a rate. With the valve in the openposition, the delivery of the drug fluid to the target may be terminatedor reduced.

Assembly and/or manufacturing of controlled delivery drive mechanism96100, drug delivery pump 9610, or any of the individual components mayutilize a number of known materials and methodologies in the art. Forexample, a number of known cleaning fluids such as isopropyl alcohol andhexane may be used to clean the components and/or the devices. A numberof known adhesives or glues may similarly be employed in themanufacturing process. Additionally, known siliconization and/orlubrication fluids and processes may be employed during the manufactureof the novel components and devices. Furthermore, known sterilizationprocesses may be employed at one or more of the manufacturing orassembly stages to ensure the sterility of the final product.

The drive mechanism may be assembled in a number of methodologies. Inone method of assembly, the drug container 9650 may first be assembledand filled with a fluid for delivery to the target. The drug container9650 includes a cap 9652, a pierceable seal 9656, a barrel 9658, and aplunger seal 9660. The pierceable seal 9656 may be fixedly engagedbetween the cap 9652 and the barrel 9658, at a distal end of the barrel9658. The barrel 9658 may be filled with a drug fluid through the openproximal end prior to insertion of the plunger seal 9660 from theproximal end of the barrel 9658. An optional connection mount 9654 maybe mounted to a distal end of the pierceable seal 9656. The connectionmount 9654 may guide the insertion of the piercing member of the fluidpathway connector into the barrel 9658 of the drug container 9650. Thedrug container 9650 may then be mounted to a distal end of drive housing96130.

One or more drive biasing members 96122 may be inserted into a distalend of the drive housing 96130. Optionally, a cover sleeve may beinserted into a distal end of the drive housing 96130 to substantiallycover biasing member 96122. A piston may be inserted into the distal endof the drive housing 96130 such that it resides at least partiallywithin an axial pass-through of the biasing member 96122 and the biasingmember 96122 is permitted to contact a piston interface surface 96110Cof piston 96110 at the distal end of the biasing member 96122. Anoptional cover sleeve may be utilized to enclose the biasing member96122 and contact the piston interface surface 96110C of piston 96110.The piston 96110 and drive biasing member 96122, and the optional coversleeve, may be compressed into drive housing 96130. Such assemblypositions the drive biasing member 96122 in an initial compressed,energized state and preferably places a piston interface surface 96110Cin contact with the proximal surface of the plunger seal 9660 within theproximal end of barrel 9658. The piston, piston biasing member, contactsleeve, and optional components, may be compressed and locked into theready-to-actuate state within the drive housing 96130 prior toattachment or mounting of the drug container 9650. The tether 96525 ispre-connected to the piston 96110 and passed through the axial apertureof the biasing member 96122 and drive mechanism housing 96130, and thenwound through the interior of the drug delivery device with the otherend of the tether 96525 wrapped around the winch drum 96520B of theregulating mechanism 96500.

A fluid pathway connector, and specifically a sterile sleeve of thefluid pathway connector, may be connected to the cap and/or pierceableseal of the drug container. A fluid conduit may be connected to theother end of the fluid pathway connector which itself is connected tothe insertion mechanism such that the fluid pathway, when opened,connected, or otherwise enabled travels directly from the drugcontainer, fluid pathway connector, fluid conduit, insertion mechanism,and through the cannula for drug delivery into the target. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform 9620 or housing 9612 of the drug delivery device, as shown inFIG. 110B.

Certain optional standard components or variations of drive mechanism96100 or drug delivery device 9610 are contemplated while remainingwithin the breadth and scope of the present disclosure. For example, theembodiments may include one or more batteries utilized to power a motoror solenoid, drive mechanisms, and drug delivery devices of the presentdisclosure. A range of batteries known in the art may be utilized forthis purpose. Additionally, upper or lower housings may optionallycontain one or more transparent or translucent windows 9618 to enablethe user to view the operation of the drug delivery device 9610 orverify that drug dose has completed. Similarly, the drug delivery device9610 may contain an adhesive patch and a patch liner on the bottomsurface of the housing 9612. The adhesive patch may be utilized toadhere the drug delivery device 9610 to the target for delivery of thedrug dose. As would be readily understood by one having ordinary skillin the art, the adhesive patch may have an adhesive surface for adhesionof the drug delivery device to the target. The adhesive surface of theadhesive patch may initially be covered by a non-adhesive patch liner,which is removed from the adhesive patch prior to placement of the drugdelivery device 9610 in contact with the target. Removal of the patchliner may further remove the sealing membrane 96254 of the insertionmechanism 96200, opening the insertion mechanism to the target for drugdelivery.

Similarly, one or more of the components of controlled delivery drivemechanism 96100 and drug delivery device 9610 may be modified whileremaining functionally within the breadth and scope of the presentdisclosure. For example, as described above, while the housing of drugdelivery device 9610 is shown as two separate components upper housing9612A and lower housing 9612B, these components may be a single unifiedcomponent. As discussed above, a glue, adhesive, or other knownmaterials or methods may be utilized to affix one or more components ofthe controlled delivery drive mechanism and/or drug delivery device toeach other. Alternatively, one or more components of the controlleddelivery drive mechanism and/or drug delivery device may be a unifiedcomponent. For example, the upper housing and lower housing may beseparate components affixed together by a glue or adhesive, a screw fitconnection, an interference fit, fusion joining, welding, ultrasonicwelding, and the like; or the upper housing and lower housing may be asingle unified component. Such standard components and functionalvariations would be appreciated by one having ordinary skill in the artand are, accordingly, within the breadth and scope of the presentdisclosure.

It will be appreciated from the above description that the controlleddelivery drive mechanisms and drug delivery devices disclosed hereinprovide an efficient and easily-operated system for automated drugdelivery from a drug container. The novel embodiments described hereinprovide drive mechanisms for the controlled delivery of drug substancesand drug delivery pumps which incorporate such controlled delivery drivemechanisms. The drive mechanisms of the present disclosure control therate of drug delivery by metering, providing resistance, or otherwisepreventing free axial translation of the plunger seal utilized to forcea drug substance out of a drug container and, thus, are capable ofdelivering drug substances at variable rates and/or delivery profiles.Additionally, the drive mechanisms of the present disclosure may provideintegrated status indication features which provide feedback to the userbefore, during, and after drug delivery. For example, the user may beprovided an initial feedback to identify that the system is operationaland ready for drug delivery. Upon activation, the system may thenprovide one or more drug delivery status indications to the user. Atcompletion of drug delivery, the drive mechanism and drug deliverydevice may provide an end-of-dose indication. The novel controlleddelivery drive mechanisms of the present disclosure may be directly orindirectly activated by the user. Furthermore, the novel configurationsof the controlled delivery drive mechanism and drug delivery devices ofthe present disclosure maintain the sterility of the fluid pathwayduring storage, transportation, and through operation of the device.Because the path that the drug fluid travels within the device isentirely maintained in a sterile condition, only these components needbe sterilized during the manufacturing process. Such components includethe drug container of the drive mechanism, the fluid pathway connector,the sterile fluid conduit, and the insertion mechanism. In at least oneembodiment of the present disclosure, the power and control system, theassembly platform, the control arm, the activation mechanism, thehousing, and other components of the drug delivery device do not need tobe sterilized. This greatly improves the manufacturability of the deviceand reduces associated assembly costs. Accordingly, the devices of thepresent disclosure do not require terminal sterilization upon completionof assembly. Furthermore, the embodiments of the present disclosurepermit device architecture and/or component integration in ways whichare not suitable for devices that require terminal sterilization. Forexample, when sterilization of the entire device is necessary, thedevice architecture often requires adequate spacing of components topermit the sterilization gas or material to effectively reach the targetsurfaces. Removing the need for terminal sterilization permits reductionor elimination of those spaces and allows for device architectures thatoffer smaller overall dimensions, human factors benefits, and/orindustrial design options that are not available for devices thatrequire terminal sterilization.

Manufacturing of a drug delivery device includes the step of attachingboth the controlled delivery drive mechanism and drug container, eitherseparately or as a combined component, to an assembly platform orhousing of the drug delivery device. The method of manufacturing furtherincludes attachment of the fluid pathway connector, drug container, andinsertion mechanism to the assembly platform or housing. The additionalcomponents of the drug delivery device, as described above, includingthe power and control system, the activation mechanism, and the controlarm may be attached, preformed, or pre-assembled to the assemblyplatform or housing. An adhesive patch and patch liner may be attachedto the housing surface of the drug delivery device that contacts theuser during operation of the device. The method of assembly of the drugdelivery device may further include positioning a safety mechanism suchas a plunger seal piercing mechanism at least partially within thebarrel and adjacent to or in contact with the plunger seal.

A method of operating the drug delivery device includes the steps of:activating, by a user, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a controlled delivery drive mechanism to drive fluiddrug flow through the drug delivery device according to a controlledrate or drug delivery profile. The method may further include the stepof: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the controlled delivery drive mechanism by theexpansion of the biasing member acting upon a piston within a drugcontainer to force fluid drug flow through the drug container, the fluidpathway connector, a sterile fluid conduit, and the insertion mechanismfor delivery of the fluid drug to the target, wherein a regulatingmechanism acting to restrain the distribution of a tether is utilized tometer the free axial translation of the piston. The method of operationof the drive mechanism and the drug delivery device may be betterappreciated with reference to FIGS. 111A-111E and FIGS. 112A-112D, asdescribed above.

XIX. Insertion Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 69A-75B, 80A-85C, 86A-91, 92A-99, 100A-109B, and110A-141B may be configured to incorporate the embodiments of theinsertion mechanism described below in connection with FIGS. 142A-152.The embodiments of the insertion mechanism described below in connectionwith FIGS. 142A-152 may be used to replace, in its entirety orpartially, the above-described insertion mechanism 200, 90200, 92200,93200, 94200, 95200, or 96200, or any other insertion mechanismdescribed herein, where appropriate.

In one embodiment, the insertion mechanism 6200 includes an insertionmechanism housing 6202 having one or more extension arms 6202A, a base6252, and a sterile boot 6250, as shown in the exploded view of FIGS.142A and 142B. Base 6252 may be connected to assembly platform 6020 tointegrate the insertion mechanism into the drug delivery device 6010 (asshown in FIG. 2B) or the or the drug delivery device 6010. Theconnection of the base 6252 to the assembly platform 6020 may be, forexample, such that the bottom of the base is permitted to pass-through ahole in the assembly platform to permit direct contact of the base tothe body of the patient. In such configurations, the bottom of the base6252 may include a sealing membrane 6254 that, at least in oneembodiment, is removable prior to use of the drug delivery device 6010or the drug delivery device 6010. Alternatively, the sealing membrane6254 may remain attached to the bottom of the base 6252 such that theneedle 6214 pierces the sealing membrane 6254 during operation of thedrug delivery device 6010 or the drug delivery device 6010. As shown inFIGS. 142A and 142B, the insertion mechanism 6200 may further include arotational biasing member 6210, a needle hub 6212, a needle 6214, aretraction biasing member 6216, a sleeve 6220, and a conduit 6218. Theconduit 6218 may connect to sterile fluid conduit 30 or to sterileaccess connection 300 to permit fluid flow through the conduit 6218,needle 6214, and into the body of the patient during drug delivery, aswill be described in further detail herein.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles. Upon assembly, the proximal end of needle6214 is maintained in fixed contact with hub 6212, while the remainderof needle 6214 is preferably located within sterile boot 6250. Theneedle 6214 may further pass-through base opening 6252E.

Sterile boot 6250 is a collapsible or compressible sterile membrane thatis in fixed engagement at a proximal end with the hub 6212 and at adistal end with the sleeve 6220 and/or base 6252. The term “sterileboot” is used to describe a boot within which certain internalcomponents may reside, at one or more stages of operation, in a sterilecondition. The boot need not be sterile through the entire operation ofthe mechanism or drug delivery device and, in fact, may not be initiallysterile until assembly and sterilization of certain components hasoccurred. Additionally, the term “boot” is not intended to mean anyspecific shape or configuration, but is instead utilized to describe acomponent that can provide an interior space within which othercomponents may reside at one or more stages of operation. In at leastone embodiment, the sterile boot 6250 is maintained in fixed engagementat a distal end between base 6252 and sleeve 6220. In other embodimentssterile boot 6250 is maintained in fixed engagement at a distal endbetween base 6252 and insertion mechanism housing 6202. Base 6252includes a base opening 6252E through which the needle may pass duringoperation of the insertion mechanism, as will be described furtherbelow. Sterility of the needle is maintained by its initial positioningwithin the sterile portions of the insertion mechanism. Specifically, asdescribed above, needle 6214 is maintained in the sterile environment ofthe sterile boot 6250. The base opening 6252E of base 6252 may be closedfrom non-sterile environments as well, such as by for example a sealingmembrane 6254.

FIGS. 143A-143B and 60-62 show the components of the insertionmechanism, according to at least a first embodiment, in greater detail.As shown in FIGS. 59A-59B, insertion mechanism housing 6202 may be asubstantially cylindrical component having an inner chamber within whichconduit 6218, hub 6212, needle 6214, sleeve 6220, retraction biasingmember 6216, and sterile boot 6250 are substantially disposed in aninitial configuration. Guide surfaces 6204 (as best seen in FIG. 143B)are located on the inner surface of housing 6202 and are configured tointeract with extension arms 6212A of hub 6212. As will be described infurther detail hereinafter rotation of housing 6202 is transferred toaxial movement of hub 6212 by interaction of guide surfaces 6204 withextension arms 6212A of hub 6212.

In order to provide rotational movement to the housing 6202, the housing6202 may further include one or more engagement surfaces 6202B disposedfor interaction with the rotational biasing member 6210. In theillustrated embodiment, the housing 6202 is provided with one or moreprotrusions 202A configured to engage a proximal end of rotationalbiasing member 6210. Protrusion 6202A may form an engagement surface202B in the form of a recess in which the proximal end of rotationalbiasing member 6210 may be disposed. In this way, unwinding and/orde-energizing of rotational biasing member 6210 causes rotation ofhousing 6202 about axis A.

Although the illustrated embodiments show the rotational biasing memberengaging protrusion 6202A, rotation of housing 6202 and rotationalbiasing member 6210 may be coupled in any way. For example, therotational biasing member 6210 may engage a slot, aperture, or bore inhousing 6202. As in the illustrated embodiment, rotational biasingmember 6210 may be located on the outside of housing 6202 in asubstantially concentric relationship. The distal end of the rotationalbiasing member may be engaged with base 6252 or anotheraxially-stationary feature of drug delivery device 6010 such thatmovement of the distal end of rotational biasing member 6210 isrestricted.

Additionally, protrusion 6202A, or another feature of housing 6202, mayfurther contact a portion of the sterile access connection duringrotation of housing 6202. This contact, in conjunction with rotation ofhousing 6202, may be used to initiate the piercing of the pierceableseal and thereby allow the contents of the drug container to flowthrough the conduit

Hub 6212, as seen in FIG. 144, includes extension arms 6212A asdescribed above. It further includes aperture 6212B configured toreceive a portion of conduit 6218. Aperture 6212B allows conduit 6218 tobe in fluid communication with needle 6214 for delivery of the fluiddrug to the patient. Needle 6214 is securely engaged with hub 6212 bybonding, press-fit or other means known to one skilled in the art.

The central body portion 6212C of the hub 6212 is disposed to axiallytranslate within sleeve 6220, which is shown in greater detail in FIG.145. In order to control the axial movement of the hub 6212 relative tothe sleeve 6220, the hub 6212 and sleeve 6220 are provided withprotrusions 6212D and recesses configured to engage one another. In theillustrated embodiment, the protrusions 6212D of the hub 6212 areconfigured as part of the extension arms 6212A, and the sleeve 6220includes slots 6220A within which extension arms 6212A of hub 6212 areat least partially disposed during operation of the insertion mechanism.This interaction restricts the ability of hub 6212 to rotate relative tothe sleeve 6220.

Sleeve 6220, as shown in FIG. 145, includes slots 6220A within whichextension arms 6212A of hub 6212 are at least partially disposed duringoperation of the insertion mechanism. These slots restrict the abilityof hub 6212 to rotate. Sleeve 6220 further includes one or moreapertures 6220B which are configured to interface with flex arms 6252Aof base 6252. During assembly, flex arms 6252A engage apertures 6220B,thereby restricting movement of sleeve 6220 with respect to base 6252.Base 6252, as shown in FIG. 147, may further include one or more loweralignment members 6252C configured to engage one or more alignmentnotches 6220C of sleeve 6220. This engagement aligns sleeve 6220 to base6252 and limits rotation of sleeve 6220 with respect to base 6252. Base6252 may also include one or more upper alignment members 6252Dconfigured to engage face 6206 of housing 6202 during installation,thereby positioning housing 6202 with respect to base 6252.

The operation of the insertion mechanism is described herein withreference to the above components, in view of FIGS. 147-149. FIG. 147Ashows an isometric view and FIG. 147B shows a cross-sectional view ofthe insertion mechanism, according to at least one embodiment of thepresent disclosure, in a locked and ready to use stage. The proximal endof rotational biasing member 6210 is disposed in recess 6202B of housing6202 and rotational biasing member 6210 is in an energized state. Inthis initial position, hub 6212 is in a retracted, proximal positionsuch that needle 6214 does not extend past opening 6252E of base 6252.Sterile boot 6250 is in an extended configuration with one end engagedwith hub 6212 and the other engaged with shell 6220 and base 6252.Retraction biasing member 6216 is in a relatively decompressed and/orde-energized state. Extension arms 6212A of hub 6212 are located withinor substantially adjacent to proximal portion 6204A of guide surfaces6204. Coiled fluid conduit 6218 may be located proximally to hub 6212.Fluid conduit 6218 may be connected at one end to hub 6212, allowingfluid drug contents to pass from the drug container 6050 to needle 6214for delivery to the patient.

In this embodiment, retraction biasing member 6216 is disposed betweenthe hub 6212 and one or more axially-stationary elements of theinsertion mechanism in a relatively decompressed and/or de-energizedstate. Here, the axially-stationary element is a portion of the sleeve6220. It will be appreciated, however, that the axially-stationaryelements may include alternate components, such as, for example, thebase 6252, or a combination of two or more such axially-stationaryelements.

It will further be appreciated that the retraction biasing member may bealternately disposed, and may include any appropriate type of retractionbiasing member. For example, in an alternate embodiment, the retractionbiasing member may include a tension spring, as opposed to a compressionspring. In such an embodiment, the retraction biasing member may bedisposed proximally to the hub 6212 and coupled to the hub and anaxially-stationary member in a de-energized state such that axialtranslation of the hub 6212 in a distal direction energizes the tensionspring.

As will be understood by those of skill in the art, insertion mechanism6200 may be held in this initial configuration by interaction with othercomponents of drug delivery device 6010. For example, drug deliverydevice 6010 may include a NIM activation mechanism. The NIM activationmechanism may be initiated or activated by depression of activationmember 14. Alternatively, the NIM activation mechanism may include aseparate member configured for activation by the user. By way ofexample, activation member 14 may be engaged with a slide which, in aninitial configuration, prevents rotation of housing 6202 by interactionwith protrusion 6202A. Depression of trigger member 14 may displace theslide, disengaging the slide, or another component, from the protrusion6202A of housing 6202, thereby allowing rotation of housing 6202.

One example of a NIM activation mechanism is shown in FIGS. 163A-163B.The NIM activation mechanism includes: a throw arm 606, a NIM interlock608, and a NIM retainer 610. Initially, as shown in FIG. 163A, the NIMretainer 610 is positioned such that the NIM retainer 610 is in contactwith a protrusion 202A of the housing 202 such that the housing 202 isprevented from rotating about axis A, thereby preventing activation ofthe NIM 200. In the embodiment shown, the NIM retainer 610 is configuredfor rotational movement about axis B. The NIM retainer 610 may, forexample, be mounted to the housing 12 at bore 610A. For example, a pinor shaft may be disposed in bore 610A around which the NIM retainer 610may rotate. The pin or shaft may an integral portion of the housing 12or, alternatively, may be a separate component. The NIM retainer 610 isinitially prevented from rotating by contact between an arm 610B of theNIM retainer 610 with the NIM interlock 608. The NIM interlock 608 isinitially in a first position in which it is in contact with or adjacentto a lower surface 606B of the throw arm 606.

Depression of the activation mechanism 14 causes translation of thethrow arm 606. The ramped surface 606C of the throw arm 606 contacts theNIM interlock 608 and causes the NIM interlock 608 to translate in adirection substantially orthogonal to the direction of translation ofthe throw arm 606 (i.e., in the direction of the shaded arrow in FIG.163A). FIG. 24B shows the position of the throw arm 606 and NIMinterlock 608 after translation of the throw arm. As shown, in thisconfiguration, the NIM interlock is positioned adjacent to or in contactwith an upper surface 606D of the throw arm 606. The window 608A of theNIM retainer 608 is aligned with the arm 610B of the NIM retainer 610.Hence, as shown in FIG. 163B, the NIM retainer 610 is able to rotateabout axis B.

In at least one embodiment, the NIM retainer 610 is biased to rotate bya biasing member. The biasing member may be, for example, a torsionspring. Rotation of the NIM retainer 610 causes the NIM retainer 610 todisengage the protrusion 202A of the housing 202. Hence, the NIM 200 isable to activate to insert a fluid path into a patient. Alternatively,force applied to NIM retainer 610 by protrusion 202A causes rotation ofNIM retainer 610.

In other embodiments, the NIM interlock 608 may directly engage aportion of the NIM 200, such as the protrusion 202A, to initiallyprevent activation of the NIM 200. Translation of the NIM interlock 608in the direction orthogonal to the translation of the throw arm 606 maycause the NIM interlock 608 to disengage the NIM 200 and allow the NIM200 to activate.

In another embodiment, the throw arm 606 is directly engaged with aportion of the NIM whereby translation of the throw arm 606 allowsactivation of the NIM 200.

In an alternative embodiment, shown in FIGS. 2A-2B, a portion of housing6202 may have gear teeth 6208 configured to interact with a gear 6209which prevents rotation of the housing. In this configuration, the gearmay be connected to a motor 6207 which controls the rotation of the gearand therefore the housing. The housing may be able to be disengaged fromthe gear, thereby allowing free rotation of the housing in response tode-energizing of the rotational biasing member. Gear 6209 may beconnected to motor 6207 through a gear train, the gear train controllingthe relationship between rotation of motor 6207 and gear 6209.Additionally, or alternatively, an escapement mechanism may be used tocontrol rotation of the gear train.

FIG. 148A shows an isometric view and FIG. 148B shows a cross-sectionalview of an insertion mechanism in a needle inserted stage. As shown inFIG. 147A unwinding and/or de-energizing of rotational biasing member6210 causes housing 6202 to rotate about axis A. As housing 6202 rotatescontact of guide surfaces 6204 with extension arms 6212A of hub 6212causes hub 6212 to translate in the distal direction. Hub 6212 isprevented from rotating by interaction between extension arms 6212A andslots 6220A of sleeve 6220. Sleeve 6220 is connected to base 6252 byengagement of flex arms 6252B with apertures 6220B. As shown, sterileboot 6250 is permitted to collapse as housing 6202 rotates and hub 6212translates in the distal direction and inserts the needle 6214 into thebody of the patient. At this stage, shown in FIG. 147B, needle 6214 isintroduced into the body of the patient for drug delivery. Due to thedistal translation of hub 6212, retraction biasing member 6216 iscompressed or energized. Rotation of housing 6202 is preferably limitedor stopped at a position in which guide surfaces 6204 retain hub 6212 ina distal position. Rotation of housing 6202 may be stopped at thisposition by interaction between protrusion 6202A and a stop component ofthe drug delivery device 6010 or the drug delivery device 6010.Alternatively, a stop component may interact with another portion ofhousing 6202. Upon insertion of the needle 6214, the fluid pathway fromthe conduit to the body of the patient through the needle 6214 isopened. As the fluid pathway connector is made to the drug container andthe drive mechanism is activated, the fluid drug treatment is forcedfrom the drug container through the fluid pathway connector and thesterile fluid conduit into the needle 6214 for delivery into the body ofthe patient.

As shown in FIGS. 149A and 149B, upon completion of drug delivery, theneedle 6214 is retracted back (i.e., axially translated in the proximaldirection) into the insertion mechanism housing 6202. Continued rotationof housing 6202 aligns the proximal portion 6204A of guide surfaces 6204with extension arms 6212A of hub 6212 such that proximal translation ofhub 6212 is no longer restricted. In this position, retraction biasingmember 6216 is able to decompress or de-energize. Expansion of theretraction biasing member 6216 translates hub 6212, and needle 6214 towhich it is connected, axially in the proximal direction. Accordingly,activation of the insertion mechanism inserts the needle 6214 into thebody of the patient, and sequentially retracts the needle 6214 aftercompletion of drug delivery or upon some other retraction initiationmechanism.

FIGS. 150-152 show another embodiment of an insertion mechanism 7200. Asshown in FIG. 150, one end of the rotational biasing member 7210 isdisposed in a recess 7202B formed in the housing 7202 of the insertionmechanism. By engaging the housing in this way the requirement for aprotrusion extending outwardly from the housing is eliminated, therebyallowing the overall size of the insertion mechanism to be reduced.Further, as shown in FIG. 151 the sterile boot 7250 may be configured inan “accordion” configuration, which may allow the diameter of thesterile boot to be less than the sterile boot shown in previousembodiments. It may also be seen in FIG. 151 that platform 7020 may haveupwardly extending boss 7020A that aids in locating and retaining theneedle insertion mechanism. The rotational biasing member 7210 may bepositioned around the outside of boss 7020A. The needle insertionmechanism may also include cap 7222. The cap may engage the shell 7220and act to retain the components of the needle insertion mechanism inplace. Specifically, the cap may retain the conduit in position withinhousing 7202. The cap may include one or more circumferential flex arms7222A which, during installation, may flex outward in response tocontact with protrusions of the shell 7220. The flex arms may thenreturn to their natural position and thereby be retained in place withrespect to the shell as seen best in the cross-section view of FIG. 152.Also seen in FIG. 152, one or more flex arms 7020B of platform 7020 mayengage apertures 7220B of the housing 7220. This engagement retains andpositions the insertion mechanism with respect to platform 7020. Theplatform 7020 of the drug delivery device may further include lockingarms 7020B which are configured to engage apertures 7220B of the shell.This engagement retains the insertion mechanism in position with respectto the drug delivery device. The stages of operation of this embodimentmay be substantially similar to those described above (i.e.,de-energizing of the rotational biasing member leads to insertion of theneedle and de-energizing of the retraction biasing member leads toretraction of the needle).

An additional embodiment of a needle insertion mechanism is shown inFIGS. 153A-155B. In this embodiment, utilizing a rigid needle 2214 toassist in placement, a flexible cannula 2260 is inserted into the targettissue for delivery of medicament. The rigid needle 2214 may be a hollowneedle or a solid trocar. In the embodiment shown in FIGS. 153A-153C, ahollow needle is used to insert the cannula 2260. For ease ofunderstanding, structures in this embodiment are identified by thereference numbers utilized for similar structures in the embodiment ofFIGS. 1A-1C prefaced by the number “2”, or as in the embodiment of FIGS.2A-2C and 142A-152, changing the reference number from “6XXX” to “2XXX”.That is structures are identified by “2XXX” wherein the “XXX” refers tosimilar structures in the embodiment of FIGS. 1A-1C, or the similarstructures in the embodiment of FIGS. 2A-2C and 142A-152 identified by“6XXX”. Accordingly, in the absence of a specific discussion below withregard to a reference number shown in FIGS. 153A-155B, those of skill inthe art will understand that structures identified by reference numbers“2XXX” refer to the same or similar structures as discussed with regardto the embodiments of FIGS. 1A-1C, 2A-2C, and 142A-152. For the purposeof clarity, a platform is not shown in FIGS. 153A-155B, one of skill theart will understand that a platform similar to that illustrated inprevious embodiments may be used in this and subsequent embodiments.

FIG. 153A shows the insertion mechanism in an initial configurationprior to activation. In the initial configuration, flexible cannula 2260is disposed such that the rigid needle 2214 passes through the lumen ofthe flexible cannula. Additionally, the proximal end of flexible cannula2260 is in contact with, or is in proximity to, needle hub 2212. Asshown, the cannula 2260 is initially disposed within sterile boot 2250and septum 2270 is disposed in aperture 2252E in base 2252. In this way,needle 2214 and cannula 2260 are thereby maintained in an asepticcondition. The cannula may be engaged with the needle by press-fit,bonding, or any other joining method. The needle may be further retainedand/or located in the hub 2212 by retainer 2290. Upon activation of theinsertion mechanism, rotation of housing 2202, caused by de-energizingof rotational biasing member 2210, causes needle hub 2212 to translatein the distal direction. This translation may be guided by contact offollowers/arms 2212A of hub 2212 with guide surfaces 2204 on theinterior of housing 2202 as described above and as shown in FIGS.154A-154B. Translation of needle hub 2212 causes needle 2214 and cannula2260 to also translate in the distal direction, pierce septum 2270, andbe inserted into the target tissue. FIG. 153B shows the insertionmechanism at the completion of the insertion step.

As the housing 2202 continues to rotate, for example, under the force ofthe rotational biasing member 2210, the secondary rotation of thehousing 2202 relatively positions the housing 2202 and the hub 2212 topermit the retraction biasing member 2216 to at least partiallyde-energize. In other words, this further rotation of housing 2202aligns extension arms 2212A of hub 2212 with axial slot 2208 of housing2202. In this position, retraction biasing member 2216 is able tode-energize or decompress, causing hub 2212 and needle 2214 to translatein the proximal direction. FIG. 153C shows the insertion mechanism atthe completion of this step. Cannula 2260 is maintained in the insertedposition and in the target tissue and needle 2214 is at least partiallydisposed within the cannula. This creates a fluid path through conduit2218, needle 2214, and cannula 2260 for delivery of the medicament tothe target tissue. Because only the flexible cannula 2260 is disposedwithin the target tissue, the cannula 2260 may flex in response tomovement. This may provide advantages in patient comfort. Barb 2260A ofcannula 2260 may be configured to engage septum 2270 and thereby resistretraction of the cannula 2260 into the insertion mechanism. Optionally,the needle 2214 may be partially disposed in the target tissue when inthis position.

In addition to the advantages described above, the insertion mechanismsdescribed herein may also be capable of terminating flow of medicamentto the target tissue by disconnecting the fluid path. This may be animportant safety feature to protect the patient. For example, somemedicaments, such as insulin, can be dangerous, and potentially evendeadly, when administered in too large a quantity and/or at too rapid ofa rate. By providing such automatic safety stop mechanisms, so-called“run-away” delivery of medicament may be prevented, thereby ensuring thesafety of the patient. While the methods and associated structures forterminating flow may be discussed with regard to one or more specificinsertion mechanisms disclosed herein, it will be appreciated that themethod and associated structures may be utilized or adapted for any ofthe insertion mechanisms disclosed herein or within the spirit and scopeof this disclosure.

An interruption in delivery of medicament to the target tissue may betriggered, for example, by an error in delivery of the medicament or byan input from the user. For example, the user may realize that they havealready taken their drug dose and wish to pause or terminate drugdelivery from the device. Upon such user input to the device, thedelivery of the drug can be stopped and/or the fluid passageway throughthe needle or cannula may be terminated by retraction of the needle toits fully retracted position, as described below.

Additionally or alternatively, the device may pause or terminate drugdelivery if it receives an error alert during operation. For example, ifthe drive mechanism is not functioning correctly, the needle insertionmechanism may be triggered to retract fully and terminate drug deliveryto the target tissue to prevent over-delivery of a medication to thetarget tissue. This capability of the needle insertion mechanismprovides a valuable safety feature for drug delivery to a user.

In some embodiments, retraction is activated upon removal of the drugdelivery device from the patient's body. In other embodiments,retraction is activated if it is determined that an error has occurredin the delivery of the substances to the patient. For example, anocclusion of the drug delivery pathway which prevents the flow ofmedicament may be detected by a sensing function of the drug deliverydevice. Upon the sensing of the occlusion an electrical or mechanicalinput may be used to initiate retraction of the needle.

Activating retraction of the needle may be accomplished through manymechanisms. For example, a button may be provided on the outside ofhousing 6012 which, when depressed by the patient, activates retractionof the needle from the patient's body. For example, in one embodiment,depressing the button may allow housing 6202 to rotate, hence allowingretraction biasing member 6216 to expand and retract needle 6214.Actuation of the button may be spring assisted such that the traveland/or force required to depress the button is reduced. Alternatively,or additionally, upon drive mechanism 6100 reaching end-of-dose anelectrical or mechanical actuator may cause activation of retraction.For example, upon end-of-dose, an electrical connection may be made suchthat a current is applied to a nitinol component. Upon application ofthe current the nitinol component's temperature rises. Because ofnitinol's shape memory characteristics this component may be configured,upon an increase in temperature, to transform from a first configurationto a second configuration. In this second configuration, the nitinolcomponent may allow or cause the actuation of the retraction of theneedle by, for example, allowing rotation of housing 6202.

Alternatively, or additionally, a sensor such as on-body sensor 24 may,when drug delivery device 6010 is removed from the patient's body, causeor allow activation of the retraction of the needle. For example, whendrug delivery device 6010 is installed on the patient the position ofon-body sensor 24 may prevent rotation of housing 6202 to the retractionposition. Upon removal from the patient a change in configuration ofon-body sensor 24 may allow rotation. In another embodiment, a lightsensor may be placed on drug delivery device 6010 near to base opening6252. When drug delivery device 6010 is in place on the patient's bodylight would be substantially blocked from entering the light sensor.Upon removal of drug delivery device 6010 from the patient's body lightmay be sensed by the light sensor and the light sensor may trigger anelectromechanical actuator to allow or cause activation of retraction.In other embodiments, a pin-type press-fit interconnect is used toinitiate retraction of the needle. The pin may be biased to at leastpartially protrude from housing 6012 and be displaced upon placement ofdrug delivery device 6010 on the patient. When displaced, the pin mayengage a female hole on a PCB which may be a part of power and controlsystem 6400. Upon removal of drug delivery device 6010 from the patient,the biased pin disengages the female PCB hole, thereby causing a signalto activate the retraction of the needle.

Retraction of the needle and/or cannula may further be initiated upon afailure and/or fault of drive mechanism 100. For example, the drivemechanism may include a tether which serves to meter or control the rateof delivery of the contents of drug container 50. The tension appliedto, or sustained by, the tether may be monitored by one or more sensors.A reduction in the tension of the tether may be an indication that thetether is not properly metering or controlling the delivery of themedicament. The sensor may be a mechanical component or linkage which isin contact with a portion of the tether, the contact at least partiallycontrolling the position and/or configuration of the sensor. In aresponse to a reduction in tension in the tether, the sensor transformsfrom a first position to a second position. This transformation may,directly or indirectly, cause retraction of the needle and/or cannula.The retraction may be caused by a purely mechanical action or,alternatively, may involve an electrical signal received and/orgenerated by power and control system 400.

In other embodiments, the sensor may be a strain gauge, load cell, forcesensor or other sensor which is configured to measure and/or monitor thestrain, load, or tension present in the tether. In these embodiments,the sensor is at least partially affixed to the tether and generates anelectrical signal based on the tension of the tether. The electricalsignal may vary in magnitude in proportion to the magnitude of tensionin the tether. Alternatively, the signal may be either interrupted orinitiated when the tension in the tether falls below or exceeds aspecified magnitude. The signal may be monitored by the power andcontrol system which, based on the presence, absence, or magnitude ofthe signal, may cause or allow the retraction of the needle and/orcannula.

In still other embodiments, a mechanical failure of the tether maydirectly cause an electrical signal to be initiated or interrupted. Forexample, the tether may be constructed, at least partially, from aconductive material. The tether may be in electrical communication withthe power and control system. The mechanical failure of the tether mayinterrupt a current path through the tether and cause a change in theflow of current in one or more circuits. This change may initiate orallow the retraction of the needle and/or cannula.

Additionally, or alternatively, the position and/or velocity of one ormore features of the drive system may be monitored by a sensor such as:an optical sensor, such as an encoder; a potentiometer; or a transducer.If the position and/or velocity of the monitored feature exceeds orfalls below a specified threshold, the power and control system mayinitiate and/or allow retraction of the needle and/or cannula.

In one example, in the embodiment shown in FIGS. 153A-153C, flow ofmedicament to the target tissue can be terminated by retracting needle2214 from cannula 2260. FIG. 16A shows a detail view of the needle 2214in a delivery position. In this position, the needle 2214 is at leastpartially disposed within the cannula 2260, thereby creating a fluidpath through the conduit, needle, and cannula and into the targettissue. FIG. 155B shows a detail view of a configuration in which theneedle 2214 has been retracted such that it is no longer disposed withinthe cannula 2260. That is, as the housing 2200 is continued to rotate,for example, under the force of the rotation biasing member 2210, thistertiary rotation of the housing 2200 aligns the followers 2212A withretraction apertures 2207 in the housing 2200, allowing the retractionbiasing member 2216 to further de-energize and move the needle 2214 to afully retracted position. Because the needle 2214 is no longer disposedwithin the cannula 2260, a fluid path does not exist for delivery ofmedicament to the target tissue. Any additional fluid that passesthrough the conduit 2218 will be discharged through the needle 2214 tothe interior of the drug pump, for example within sterile boot 2250. Abarrier 2280 may be included to further prevent any medicament fromentering cannula 2260 after retraction of the needle from the cannula.The barrier 2280 may be, for example, a septum which is pierced by theneedle during assembly of the needle and cannula. Alternatively, thebarrier 2280 may be a membrane or a clip which is displaced by theneedle during assembly but which, upon retraction of the needle from thecannula, substantially covers the lumen of the cannula. A pressuredifferential within the cannula may also prevent the flow of medicamentthere-through after retraction of the needle, with or without theutilization of a barrier 2280.

As shown in FIGS. 164A-164B, the secondary or tertiary rotation of thehousing may be controlled by a NIM retraction mechanism. In one exampleof a NIM retraction mechanism, with the needle and needle hub in thedelivery position, protrusion 202A may be in contact with stop member620, as shown in FIG. 164A. In this position, stop member 620 isprevented from rotating about spindle 624 by contact with slide member622. Thus, further rotation of housing 202 is prevented. For example, inembodiments having a flexible cannula, such as that shown in FIGS.153A-153C and described above, or as shown in FIGS. 156A-161 anddescribed below, this position may correspond with the positionsillustrated in FIG. 153C and FIG. 157C, respectively. In response to atriggering mechanism, slide member 622 may be displaced such that stopmember 620 is able to rotate, about spindle 624, to the position shownin FIG. 164B. Hence, stop member 620 no longer restricts rotation ofhousing 202, allowing the needle to be fully retracted to a position inwhich medicament is no longer delivered to the target tissue, such asthat shown in FIG. 155B and FIG. 156D. The triggering mechanism thatcauses displacement of slide member 622 may, for example, be caused byuser input, a fault of the operation of the drug pump or any other eventdescribed above. In addition, displacement of slide member 622 may bepurely mechanical or, alternatively, may be occur at least partially inresponse to a signal from power and control system 400.

Another embodiment is shown in FIGS. 156A-161. As in the embodiment ofFIGS. 153A-153C described above, the present embodiment is configured toinsert a flexible cannula into the target. For ease of understanding,structures in this embodiment are identified by the reference numbersutilized for similar structures in the embodiment of FIGS. 1A-1Cprefaced by the number “3”, or as in the embodiment of FIGS. 153A-155B,changing the reference number from “2XXX” to “3XXX”. That is structuresare identified by “3XXX” wherein the “XXX” refers to similar structuresin the embodiment of FIGS. 1A-1C, or the similar structures in theembodiment of FIGS. 153A-155B identified by “2XXX”. Accordingly, in theabsence of a specific discussion below with regard to a reference numbershown in FIGS. 156A-161, those of skill in the art will understand thatstructures identified by reference numbers “3XXX” refer to the same orsimilar structures as discussed with regard to the previous embodiments.

The stages of operation are shown in three different cross-sections inFIGS. 156-158, while individual components clip 3286, cannula retainer3282, needle hub 3212, and housing 3202 are illustrated in FIGS.159-162, respectively. The first cross-section, shown in FIGS.156A-156D, shows the interaction of followers 3212A of needle hub 3212with guide surfaces 3204 of the housing 3202 at various stages ofoperation. Initially, as shown in FIG. 156A, hook arm 3212C is engagedwith notch 3202C of housing 3202. This allows proper positioning andalignment of needle hub 3212 with respect to housing 3202.

Rotation of the housing, caused by de-energizing of rotational biasingmember 3210, disengages hook arm 3212C from notch 3202C. Furtherrotation of housing 3202, and contact between followers 3212A and guidesurfaces 3204, causes needle hub 3212 to translate in the distaldirection until needle 3214 and cannula 3260 are fully inserted in thetarget as shown in FIG. 156B.

After insertion of the needle 3214 and cannula 3260, continued, that is,secondary rotation of housing 3202 aligns axial slot 3208 of housing3202 with followers 3212A. Hence, retraction biasing member 3216 is ableto de-energize, which causes proximal translation of needle hub 3212 tothe at least partially retracted position as shown in FIG. 156C. In thisposition, needle 3214 is at least partially disposed in cannula 3260 andthrough septum 3284 and followers 3212A are in contact with proximalportion 3204A of guide surfaces 3204. Therefore, contents may bedelivered through needle 3214, cannula 3260, and to the target tissue.

In order to terminate delivery of medicament to the target tissue,continued rotation of housing 3202 may cause needle 3214 to be furtherretracted to the position shown in FIG. 156D. That is, as the housing3200 is continued to rotate, for example, under the force of therotation biasing member 3210, this tertiary rotation of the housing 3200causes followers 3212A to disengage proximal portion 3204A and bealigned with retraction aperture 3207, thereby allowing additionalproximal translation of needle hub 3212 in response to de-energizing ofretraction biasing member 3216. In this position, needle 3214 iswithdrawn from septum 3284. Hence, contents that flow through needle3214 are not able to enter cannula 3260. Retraction of the needle may becaused by any of the safety mechanisms described, such as, for example,the safety mechanism illustrated in FIGS. 164A and 164B.

The second cross-section, shown in FIGS. 157A-157C, shows theinteraction of connection arms 3286A of clip 3286 with needle hub 3212.The clip 3286 and the needle hub 3212 are shown in more detail in FIGS.159 and 161, respectively. Initially, as seen in FIG. 1157A, connectionarms 3286A are engaged with needle hub 3212, thereby coupling axialtranslation of clip 3286 and needle hub 3212. As seen in FIG. 1157B,connection arms 3286A remain engaged with needle hub 3212 as needle 3214and cannula 3260 are inserted into the target. As will be describedbelow, and as best seen in FIGS. 158A-158C, as clip 3286 translates inthe distal direction it engages flex arms 3220D of sleeve 3220. Due tothis engagement, clip 3286 is prevented from translating in the proximaldirection. Hence, upon alignment of followers 3212A with proximalportion 3204A of guide surfaces 3204, connection arms 3286A disengagefrom needle hub 3212 by flexing outward (i.e., in the direction of thehatched arrows in FIG. 157C). As a result, upon alignment of followers3212A with proximal portion 3204A of guide surfaces 3204, needle hub3212 and needle 3214 translate in the proximal direction and needle 3214is at least partially withdrawn from the target. Cannula 3260 remainsdisposed within the target.

The third cross-section is shown in FIGS. 158A-158C. The interactionbetween flex arms 3220D of sleeve 3220 and clip 3286 may be seen inthese figures. As clip 3286 is translated distally during needle andcannula insertion, clip 3286 comes in contact with flex arms 3220D andcauses them to be displaced outward (i.e., in the direction of the solidarrows shown in FIG. 158A). As shown in FIG. 158B, continued distaltranslation of clip 3286 allows flex-arms 3220D to at least partiallyreturn to their initial positions. As shown in FIG. 158C, as biasingmember 3216 begins to expand, translation of clip 3286 is restricted bycontact with flex arms 3220D. This restriction causes cannula 3260 toremain disposed within the target. As shown in FIG. 149, clip 3286 mayinclude ramped surfaces 3286B configured to engage flex-arms 3320D. Theramped surfaces may create an undercut which ensures that contact oframped surfaces 3286B with flex arms 3320D does not cause outwardflexion of flex-arms 3320D.

As shown in FIG. 160, cannula retainer 3282 includes bore 3282B and pins3282A. As assembled, a shoulder of cannula 3260 and septum 3284 aredisposed within bore 3282B. They are retained in this position by theposition of clip 3286. Pins 3282A are configured to engage holes 3286Dof clip 3286. This engagement may be configured to be a press-fitengagement to maintain the relative positions of cannula retainer 3282and clip 3286. The central hole 3286C of the clip 3286 is adapted toreceive needle 3214.

Certain optional standard components or variations of insertionmechanism 6200 or the drug delivery devices 6010 are contemplated whileremaining within the breadth and scope of the present disclosure. Forexample, upper or lower housings may optionally contain one or moretransparent or translucent windows 18, as shown in FIGS. 1A-1C, toenable the patient to view the operation of the drug delivery device6010 or verify that drug dose has completed. Additionally, the drugdelivery device 6010 may contain an adhesive patch and a patch liner onthe bottom surface of the housing 6012. The adhesive patch may beutilized to adhere the drug delivery device 6010 to the body of thepatient for delivery of the drug dose. As would be readily understood byone having ordinary skill in the art, the adhesive patch may have anadhesive surface for adhesion of the drug delivery device to the body ofthe patient. The adhesive surface of the adhesive patch may initially becovered by a non-adhesive patch liner, which is removed from theadhesive patch prior to placement of the drug delivery device 6010 incontact with the body of the patient. Adhesive 26 may optionally includea protective shroud that prevents actuation of the optional on-bodysensor 24 and covers base opening 6252E. Removal of the patch liner mayremove the protective shroud or the protective shroud may be removedseparately. Removal of the patch liner may further remove the sealingmembrane 6254 of the insertion mechanism 6200, opening the insertionmechanism to the body of the patient for drug delivery.

Similarly, one or more of the components of insertion mechanism 6200 andthe drug delivery devices 6010 and 6010 may be modified while remainingfunctionally within the breadth and scope of the present disclosure. Forexample, as described above, while the housing of drug delivery device6010 is shown as two separate components upper housing 12A and lowerhousing 12B, these components may be a single unified component. Asdiscussed above, a glue, adhesive, or other known materials or methodsmay be utilized to affix one or more components of the insertionmechanism and/or drug delivery device to each other. Alternatively, oneor more components of the insertion mechanism and/or drug deliverydevice may be a unified component. For example, the upper housing andlower housing may be separate components affixed together by a glue oradhesive, a screw fit connection, an interference fit, fusion joining,welding, ultrasonic welding, and the like; or the upper housing andlower housing may be a single unified component. Such standardcomponents and functional variations would be appreciated by one havingordinary skill in the art and are, accordingly, within the breadth andscope of the present disclosure.

It will be appreciated from the above description that the insertionmechanisms and drug delivery devices disclosed herein provide anefficient and easily-operated system for automated drug delivery from adrug container. The novel embodiments described herein provideintegrated safety features; enable direct patient activation of theinsertion mechanism; and are configured to maintain the sterility of thefluid pathway. As described above, the integrated safety featuresinclude optional on-body sensors, redundant lock-outs, automated needleinsertion and retraction upon patient activation, and numerous patientfeedback options, including visual and auditory feedback options. Thenovel insertion mechanisms of the present disclosure may be directlyactivated by the patient. For example, in at least one embodiment therotation prevention feature, whether it is a stop component configuredto engage protrusion 6202A or a gear engaged with teeth of housing 6202,which maintain the insertion mechanism in its locked, retracted state isdirectly displaced from its locked position by patient depression of theactivation mechanism. Alternatively, one or more additional componentsmay be included, such as a spring mechanism, which displaces therotation prevention feature upon direct displacement of the activationmechanism by the patient without any intervening steps. In at least oneconfiguration, rotation of a motor causes or allows rotation of a gear,thereby allowing rotation of the housing of the insertion mechanism.

Furthermore, the novel configurations of the insertion mechanism anddrug delivery devices of the present disclosure maintain the sterilityof the fluid pathway during storage, transportation, and throughoperation of the device. Because the path that the drug fluid travelswithin the device is entirely maintained in a sterile condition, onlythese components need be sterilized during the manufacturing process.Such components include the drug container of the drive mechanism, thefluid pathway connector, the sterile fluid conduit, and the insertionmechanism. In at least one embodiment of the present disclosure, thepower and control system, the assembly platform, the control arm, theactivation mechanism, the housing, and other components of the drugdelivery device do not need to be sterilized. This greatly improves themanufacturability of the device and reduces associated assembly costs.Accordingly, the devices of the present disclosure do not requireterminal sterilization upon completion of assembly. A further benefit ofthe present disclosure is that the components described herein aredesigned to be modular such that, for example, the housing and othercomponents of the drug delivery device may readily be configured toaccept and operate insertion mechanism 6200 or a number of othervariations of the insertion mechanism described herein.

Assembly and/or manufacturing of insertion mechanism 6200, drug deliverydevice 6010, or any of the individual components may utilize a number ofknown materials and methodologies in the art. For example, a number ofknown cleaning fluids such as isopropyl alcohol may be used to clean thecomponents and/or the devices. A number of known adhesives or glues maysimilarly be employed in the manufacturing process. Additionally, knownsiliconization fluids and processes may be employed during themanufacture of the novel components and devices. Furthermore, knownsterilization processes may be employed at one or more of themanufacturing or assembly stages to ensure the sterility of the finalproduct.

In a further embodiment, the present disclosure provides a method ofassembling the insertion mechanism including the steps of: connecting ahub to a proximal end of a needle; connecting a conduit to the hub;connecting a sterile boot to the hub; inserting a retraction biasingmember into a sleeve of the needle insertion mechanism; inserting thehub, needle, conduit, and sterile boot into the sleeve (in thisposition, the retraction biasing member is constrained between the hubat one end and the shell at the other end); placing a housing around thesleeve; inserting a retraction biasing member into the sleeve; andconnecting a base to the sleeve by engagement of flex arms withapertures in the housing. A rotational biasing member may be placedaround the housing such that a portion of the rotational biasing memberis engaged with a portion of the housing, thereby coupling de-energizingof the biasing member with rotation of the housing.

The distal end of the sterile boot may be positioned and held in fixedengagement with the distal end of the insertion mechanism housing byengagement of the housing with a base. In this position, the sterileboot is in an expanded configuration around the needle and creates anannular volume which may be sterile. A fluid conduit may be connected tothe hub such that the fluid pathway, when open, travels directly fromthe fluid conduit, through the hub, and through the needle. A fluidpathway connector may be attached to the opposite end of the fluidconduit. The fluid pathway connector, and specifically a sterile sleeveof the fluid pathway connector, may be connected to a cap and pierceableseal of the drug container. The plunger seal and drive mechanism may beconnected to the drug container at an end opposing the fluid pathwayconnector. A sealing membrane may be attached to the bottom of the baseto close off the insertion mechanism from the environment. Thecomponents which constitute the pathway for fluid flow are nowassembled. These components may be sterilized, by a number of knownmethods, and then mounted either fixedly or removably to an assemblyplatform or housing of the drug delivery device.

Manufacturing of a drug delivery device includes the step of attachingthe base of the insertion mechanism to an assembly platform or housingof the drug delivery device. In at least one embodiment, the attachmentis such that the base of the insertion mechanism is permitted topass-through the assembly platform and/or housing to come in directcontact with the body of the patient. The method of manufacturingfurther includes attachment of the fluid pathway connector, drugcontainer, and drive mechanism to the assembly platform or housing. Theadditional components of the drug delivery device, as described above,including the power and control system, the activation mechanism, andthe control arm may be attached, preformed, or pre-assembled to theassembly platform or housing. An adhesive patch and patch liner may beattached to the housing surface of the drug delivery device thatcontacts the patient during operation of the device.

A method of operating the drug delivery device may include the steps of:activating, by a patient, the activation mechanism; displacing a controlarm to actuate an insertion mechanism; and actuating a power and controlsystem to activate a drive control mechanism to drive fluid drug flowthrough the drug delivery device. The method may further include thestep of: engaging an optional on-body sensor prior to activating theactivation mechanism. The method similarly may include the step of:establishing a connection between a fluid pathway connector to a drugcontainer. Furthermore, the method of operation may include translatinga plunger seal within the drive control mechanism and drug container toforce fluid drug flow through the drug container, the fluid pathwayconnector, a sterile fluid conduit, and the insertion mechanism fordelivery of the fluid drug to the body of a patient.

XX. Additional Embodiments of Insertion Mechanism

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-2B, 33A-33C, 69A-75B, 80A-85C, 86A-91, 92A-99, 100A-109B, and110A-141B may be configured to incorporate the embodiments of theinsertion mechanism described below in connection with FIGS. 33A-33C.The embodiments of the insertion mechanism described below in connectionwith FIGS. 33A-33C may be used to replace, in its entirety or partially,the above-described insertion mechanism 200, 6200, 7200, 90200, 92200,93200, 94200, 95200, or 96200, or any other insertion mechanismdescribed herein, where appropriate.

A number of insertion mechanisms may be utilized within the drugdelivery devices of the present disclosure. The pump-type deliverydevices of the present disclosure may be connected in fluid flowcommunication to a patient or patient, for example, through any suitablehollow tubing. A solid bore needle may be used to pierce the skin of thepatient and place a hollow cannula at the appropriate delivery position,with the solid bore needle being removed or retracted prior to drugdelivery to the patient. As stated above, the fluid can be introducedinto the body through any number of means, including but not limited to:an automatically inserted needle, cannula, micro-needle array, orinfusion set tubing. A number of mechanisms may also be employed toactivate the needle insertion into the patient. For example, a biasingmember such as a spring may be employed to provide sufficient force tocause the needle and cannula to pierce the skin of the patient. The samespring, an additional spring, or another similar mechanism may beutilized to retract the needle from the patient. In a preferredembodiment, the insertion mechanism may generally be as described inInternational Patent Application No. PCT/US2012/53174, which is includedby reference herein in its entirety for all purposes. Such aconfiguration may be utilized for insertion of the drug delivery pathwayinto, or below, the skin (or muscle) of the patient in a manner thatminimizes pain to the patient. Other known methods for insertion of afluid pathway may be utilized and are contemplated within the bounds ofthe present disclosure, including a rigid needle insertion mechanismand/or a rotational needle insertion mechanism as described by thepresent disclosure.

In at least one embodiment, the insertion mechanism 8200 includes aninsertion mechanism housing having one or more lockout windows, and abase for connection to the assembly platform and/or pump housing (asshown in FIG. 33B and FIG. 33C). The connection of the base to theassembly platform 8020 may be, for example, such that the bottom of thebase is permitted to pass-through a hole in the assembly platform topermit direct contact of the base to the body of the patient. In suchconfigurations, the bottom of the base may include a sealing membranethat is removable prior to use of the drug delivery device 8000. Theinsertion mechanism may further include one or more insertion biasingmembers, a needle, a retraction biasing member, a cannula, and amanifold. The manifold may connect to sterile fluid conduit 8030 topermit fluid flow through the manifold, cannula, and into the body ofthe patient during drug delivery.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles more commonlyreferred to as “trocars.” In a preferred embodiment, the needle is a 27gauge solid core trocar and in other embodiments, the needle may be anysize needle suitable to insert the cannula for the type of drug and drugadministration (e.g., subcutaneous, intramuscular, intradermal, etc.)intended. A sterile boot may be utilized within the needle insertionmechanism. The sterile boot is a collapsible sterile membrane that is infixed engagement at a proximal end with the manifold and at a distal endwith the base. In at least on embodiment, the sterile boot is maintainedin fixed engagement at a distal end between base and insertion mechanismhousing. Base includes a base opening through which the needle andcannula may pass-through during operation of the insertion mechanism, aswill be described further below. Sterility of the cannula and needle aremaintained by their initial positioning within the sterile portions ofthe insertion mechanism. Specifically, as described above, needle andcannula are maintained in the sterile environment of the manifold andsterile boot. The base opening of base may be closed from non-sterileenvironments as well, such as by for example a sealing membrane (notvisible).

According to at least one embodiment of the present disclosure, theinsertion mechanism is initially locked into a ready-to-use stage bylockout pin(s) which are initially positioned within lockout windows ofthe insertion mechanism housing. In this initial configuration,insertion biasing member and retraction biasing member are each retainedin their compressed, energized states. Displacement of the lockoutpin(s), by one or more methods such as pulling, pushing, sliding, and/orrotation, permits insertion biasing member to decompress from itsinitial compressed, energized state. This decompression of the insertionbiasing member drives the needle and, optionally, the cannula into thebody of the patient. At the end of the insertion stage or at the end ofdrug delivery (as triggered by the multi-function drive mechanism), theretraction biasing member is permitted to expand in the proximaldirection from its initial energized state. This axial expansion in theproximal direction of the retraction biasing member retracts the needle.If an inserter needle/trocar and cannula configuration are utilized,retraction of the needle may occur while maintaining the cannula influid communication with the body of the patient. Accordingly, theinsertion mechanism may be used to insert a needle and cannula into thepatient and, subsequently, retract the needle while retaining thecannula in position for drug delivery to the body of the patient.

XXI. Fill Finish Cartridge

The sterile fluid pathway assemblies described above may be filled withpharmaceutical treatments, such as the drugs described below, usingstandard filling equipment and systems. This advantage is enabled by thefill-finish cartridges described below which function to maintain thesterility of the fluid pathway assemblies and allow them to nest, mount,or otherwise be removably inserted into trays for standard fill-finishprocesses, as discussed further below. The drive mechanisms, fluidpathway connectors, insertion mechanisms, and other components andsubcomponents of the drug delivery devices described below in connectionwith FIGS. 165-87 may be implemented in any of the drug delivery devicesdescribed above in connection with FIGS. 1A-164B or any other drugdelivery devices disclosed herein, where appropriate. Furthermore, anyof the methods of manufacture and methods of use described below may beapplied to the drug delivery devices described above in connection withFIGS. 1A-164B or any other drug delivery devices disclosed herein, whereappropriate.

Turning to FIG. 165, there is illustrated a schematic representation ofan example of a drug delivery device 10 incorporating aspects of thedisclosure. The device 10 includes a housing 612 having an activationmechanism 614. For ease of understanding, the housing 612 is shownschematically. In accordance with the disclosure, the device furtherincludes a fill-finish cartridge 616. The fill-finish cartridge 616includes a drug container 618, a fluid pathway assembly 620 including afluid pathway connector 622 and a needle insertion mechanism 624. Thefluid pathway assembly 620 may include further structure thatfacilitates disposition of various components, including, for example, afluid conduit 26. The fluid pathway connector 622 is disposedsubstantially adjacent a distal end 628 of the drug container 618, andthe needle insertion mechanism 624 is disposed substantially adjacent adistal end 630 of the fluid pathway connector 622. In the illustratedembodiment, the drug container 618 is generally horizontally positionedand perpendicular from a vertically positioned needle insertionmechanism 624. It will be appreciated, however, that the components maybe positioned in any appropriate manner.

Administration of a drug contained in the drug container 618 may beinitiated by the activation mechanism 614. The activation mechanism 614may include, for example, activation mechanisms that are manuallyactuated by a patient, or that are automatically actuated by, forexample, a power and control module 632 that may include, by way offurther example, a microprocessor or other automatic administrationarrangement with appropriate connections. In this embodiment, theactivation mechanism 614 is a button 634 that may be disposed, forexample, along an outer surface of the housing 612, and may beselectively depressed by the patient. It will be appreciated that thedrug delivery device 10 as well as the activation mechanism 614 may beof any appropriate design.

The power and control module 632, if included, may include a powersource, which provides the energy for various electrical componentswithin the drug delivery device, one or more feedback mechanisms, amicrocontroller, a circuit board, one or more conductive pads, and oneor more interconnects. Other components commonly used in such electricalsystems may also be included, as would be appreciated by one havingordinary skill in the art. The one or more feedback mechanisms mayinclude, for example, audible alarms such as piezo alarms and/or lightindicators such as light emitting diodes (LEDs). The microcontroller maybe, for example, a microprocessor. The power and control module 632controls several device interactions with the patient and may interfacewith one or more other components of the drug delivery device 10. In oneembodiment, the power and control module 632 may identify when anon-body sensor and/or the activation mechanism 614 have been activated.The power and control module 632 may also interface with a statusindicator, which may be a transparent or translucent material whichpermits light transfer, to provide visual feedback to the patient. Thepower and control module 632 may interface with a drive mechanism and/orthe integrated sterile fluid pathway connector and drug container 618through one or more interconnects to relay status indication, such asactivation, drug delivery, and/or end-of-dose, to the patient. Suchstatus indication may be presented to the patient via tactile feedback,such as vibration; auditory tones, such as through the audible alarms;and/or via visual indicators, such as through the LEDs. In a preferredembodiment, the control interfaces between the power and control systemand the other components of the drug delivery device are not engaged orconnected until activation by the patient. This is a desirable safetyfeature that prevents accidental operation of the drug delivery deviceand may also maintain the energy stored in the power source duringstorage, transport, and the like.

The power and control module 632 may be configured to provide a numberof different status indicators to the patient. For example, the powerand control module 632 may be configured such that after the on-bodysensor and/or trigger mechanism have been pressed, the power and controlmodule 632 provides a ready-to-start status signal via the statusindicator if device start-up checks provide no errors. After providingthe ready-to-start status signal and, in an embodiment with the optionalon-body sensor, if the on-body sensor remains in contact with the bodyof the patient, the power and control module 632 will power the drivemechanism to begin delivery of the drug treatment through the integratedsterile fluid pathway connector 622 and sterile fluid conduit 26. In apreferred embodiment of the present disclosure, the insertion mechanism624 and the drive mechanism may be caused to activate directly bypatient operation of the activation mechanism 614. The integratedsterile fluid pathway connector is connected (i.e., the fluid pathway isopened) by the pneumatic force of the drug fluid within the drugcontainer 618 created by activation of the drive mechanism, as isdetailed further herein. During the drug delivery process, the power andcontrol module 632 is configured to provide a dispensing status signalvia the status indicator. After the drug has been administered into thebody of the patient and after the end of any additional dwell time, toensure that substantially the entire dose has been delivered to thepatient, the power and control module 632 may provide an okay-to-removestatus signal via the status indicator. This may be independentlyverified by the patient by viewing the drive mechanism and delivery ofthe drug dose within the drug container through a window of the housing612. Additionally, the power and control module 632 may be configured toprovide one or more alert signals via the status indicator, such as forexample alerts indicative of fault or operation failure situations.

Other power and control system configurations may be utilized with thenovel drug delivery devices of the present disclosure. For example,certain activation delays may be utilized during drug delivery. Asmentioned above, one such delay optionally included within the systemconfiguration is a dwell time which ensures that substantially theentire drug dose has been delivered before signaling completion to thepatient. Similarly, activation of the device may require a prolongeddepression (i.e., pushing) of the activation mechanism 614 of the drugdelivery device 10 prior to drug delivery device activation.Additionally, the system may include a feature which permits the patientto respond to the end-of-dose signals and to deactivate or power-downthe drug delivery device. Such a feature may similarly require a delayeddepression of the activation mechanism, to prevent accidentaldeactivation of the device. Such features provide desirable safetyintegration and ease-of-use parameters to the drug delivery devices. Anadditional safety feature may be integrated into the activationmechanism to prevent partial depression and, therefore, partialactivation of the drug delivery devices. For example, the activationmechanism and/or power and control system may be configured such thatthe device is either completely off or completely on, to prevent partialactivation. Such features are described in further detail hereinafterwith regard to other aspects of the novel drug delivery devices.

When included, the power and control module 632 may include a processor(not shown) and a memory component (not shown). The processor may bemicroprocessors or other processors as known in the art. In someembodiments the processor may be made up of multiple processors. Theprocessor may execute instructions for generating administration signaland controlling administration of a drug contained in the drug container618. Such instructions may be read into or incorporated into a computerreadable medium, such as the memory component or provided external toprocessor. In alternative embodiments, hard-wired circuitry may be usedin place of or in combination with software instructions to implementdrug administration. Thus, embodiments are not limited to any specificcombination of hardware circuitry and software.

The term “computer-readable medium” as used herein refers to any mediumor combination of media that participates in providing instructions toprocessor for execution. Such a medium may take many forms. The memorycomponent may include any form of computer-readable media as describedabove. The memory component may include multiple memory components.

The power and control module 632 may be enclosed in a single housing. Inalternative embodiments, the power and control module 632 may include aplurality of components operably connected and enclosed in a pluralityof housings.

The power and control module 632 may be configured to generate anadministration signal as a function of patient actuation, preprogrammedactuation or remote actuation. The power and control module 632 may becommunicatively coupled to fill-finish cartridge 616, and/or the drugcontainer 618, the fluid pathway connector 622, and/or the needleinsertion mechanism 624 individually.

In accordance with an aspect of embodiments of the disclosure, in theillustrated embodiment, actuation of the activation mechanism 614, here,depression of the button 634, results in engagement of the fluid pathwayconnector 622, as will be discussed in greater detail below. This sameaction by the patient may trigger the needle insertion mechanism 624 toinject a needle or cannula into the patient, as will likewise beexplained in greater detail below. Thus, actuation of activationmechanism 614 results in the completion of a drug pathway from the drugcontainer 618 through the fluid pathway connector 622, the fluid conduit26, and the needle insertion mechanism 624 to the patient (not shown).Actuation of the activation mechanism 614 may also result in a drivemechanism acting upon structure associated with the drug container 618to force fluid through the sterile pathway. In an embodiment of thepresent disclosure, the needle insertion mechanism 624 may be triggeredto retract the needle from the patient, giving a clear end of dosedelivery indication upon completion of drug delivery. The housing 612may additionally include, for example, a window through which the drugcontainer 618 may be viewed to confirm drug delivery.

According to an aspect of embodiments of the disclosure, the fill-finishcartridge 616 is constructed and filled prior to assembly into thehousing 612 of the drug delivery device 10. In this regard, thefill-finish cartridge 616 is sufficiently robust to withstand proceduresfor sterilizing the fill-finish cartridge 616, in some embodiments priorto fill, and in some embodiments after fill. After the sterileconstruction and filling of the fill-finish cartridges 616, the devicemay be positioned as needed within a drug delivery device 10. In anyevent, the sterility of the fluid pathway assembly 620 and the drugcontainer 618 are maintained through aspects of the assembly, filling,and manufacturing processes. Final assembly of the drug delivery device10 can thus be performed outside of a sterile environment. Because onlythe components of the sterile fluid pathway assembly 620 need to be, andhave been, sterilized, the remainder of the drug delivery device 10 doesnot need sterilization (i.e., terminal sterilization). This provides anumber of advantages. Novel embodiments of the present disclosure mayalso alleviate the need to fill the drug delivery device at time-of-use,although some embodiments of the present disclosure may be utilized indevices configured for time-of-use filling as well.

According to another aspect of embodiments of the disclosure, variousembodiments of individual components of the fill-finish cartridge 616may be assembled in various configurations to provide variousembodiments of the fill-finish cartridge 616. The following disclosuresdisclose exemplary structures of individual elements that may beincorporated into the fill-finish cartridge 616, and are incorporatedherein by reference for everything disclosed therein: U.S. applicationSer. No. 13/600,114 filed Aug. 30, 2012; U.S. application Ser. No.13/599,727 filed Aug. 30, 2012; U.S. application Ser. No. 13/612,203filed Sep. 12, 2012; and Ser. No. 13/796,156 filed Mar. 12, 2013. FIG.166B is a chart of examples of variables for possible structures ofconnections between individual components that may yield variousconfigurations of embodiments of fill-finish cartridges 616, while FIG.166A shows an example of a fill-finish cartridge 616 identifying aspectsreferenced in FIG. 166A. For ease of understanding, the same referencenumbers are utilized as in FIG. 165. The individual components, as wellas the interactions and connections between the individual componentsmay have various designs. For example, the needle insertion mechanism624 may be of any suitable design. Similarly, the container 618 and thefluid pathway connector 622 may each be of any appropriate design.

Likewise, the interactions between the components may be of anyappropriate design. For example, the engagement of the fluid pathwayconnector 622 with the drug container 618 may include a threaded or snapconnection, an interference fit, or an external support or otherarrangement, so long as a tight seal is obtained. Similarly, theengagement of the fluid pathway connector 622 with the needle insertionmechanism 624 may include a threaded or snap connection, an interferencefit, a tongue and groove arrangement, an external support, or some otherarrangement including, but not limited to, utilizing a fluid conduitbetween the fluid pathway connector 622 and the needle insertionmechanism 624 for the connection. Moreover, in some embodiments, theengagement of the fluid pathway connector 622 with the needle insertionmechanism 624 may be disassembled following the fill-finish process inorder to permit the needle insertion mechanism 624 to be oriented otherthan axially with the remainder of the fill-finish cartridge 616, solong as the sterile fluid connection is maintained.

In various embodiments, the fill-finish cartridge 616 may be maintainedwith the components in axial alignment during the fill-finish process,as well as in use with a drug delivery device 10. That is, for example,the needle insertion mechanism 624 may be disposed axially with theremainder of the fill-finish cartridge 616 during both the fill-finishprocess, such as is shown in FIG. 166B, and in use in a drug delivery.In other embodiments, the fill-finish cartridge 616 may be maintainedwith the components in axial alignment during the fill-finish process,such as is illustrated in FIG. 166B, while the components may bemaintained in other than axial alignment in use with a drug deliverydevice 10. For example, as illustrated in FIG. 165, the needle insertionmechanism 624 is disposed spaced from the fluid pathway connector 622and the drug container 618, and at a 90.degree. orientation. In otherembodiments, the fill-finish cartridge may be maintained with thecomponents in other than axial alignment during the fill-finish process,yet be axially aligned in use with a drug delivery device 10. In otherembodiments, the fill-finish cartridge 616 may be maintained with thecomponents in other than axial alignment during both the fill-finishprocess and in use with a drug delivery device 10.

Further, while not included in all embodiments, in order to provideadded structural integrity to the fill-finish cartridge 616, a carriermay be provided, as will be explained in more detail below. Such acarrier may be integrated with the structure of the fill-finishcartridge 616 such that it is maintained about or along at least aportion of the fill-finish cartridge 616 in the drug delivery device 10,or such a carrier may be fully or partially disposable. A carrier mayperform a number of functions, such as, the maintenance of the relativepositions of various of the fill-finish cartridge components duringassembly, a fill-finish process, or other operations performed on thefill-finish cartridge or a drug delivery device incorporating the same;a carrier or a portion of a carrier may be utilized in the interactionof the fill-finish cartridge with a drug delivery device 10, such as, inattachment of the fill-finish cartridge 616 into a drug delivery device10 or in connection with operation of a drug delivery device 10. Moredetailed explanations of various examples of such structures in variedconfigurations follow; it is not the intention to limit the structuresto those particular configurations. Rather, the individual arrangementsexplained are provided as examples of various possible configurationsand structures within the purview of this disclosure.

FIG. 167 shows an exploded view of one embodiment of the fill-finishcartridge 716 of the present disclosure. For ease of understanding, thenumber utilized in FIG. 165 are utilized in further examples ofembodiments of the disclosure with numerical prefixes; in thisembodiment, 1XX will be utilized. The fill-finish cartridge 716 of thisembodiment includes a fluid pathway assembly 720 connected to a drugcontainer 718.

The fluid pathway assembly 720 includes a needle insertion mechanism 724coupled to a fluid pathway connector 722 by a fluid conduit 726. Aproximal end of the needle insertion mechanism 724 is connected to adistal end of a fluid conduit 726, which is connected at its proximalend to the fluid pathway connector 722.

The needle insertion mechanism 724 may be of any appropriate design solong as it may be sterilized prior to the placement of the fill-finishcartridge 716 in a drug delivery device. Examples of such needleinsertion mechanisms 724 for implants and liquid drugs and are disclosedin U.S. application Ser. No. 13/599,727 filed Aug. 30, 2012, isincorporated herein by reference for everything disclosed therein. Itwill be noted that the needle insertion mechanism 724 of FIG. 167includes an axial structure, such that the administration needle (notvisible in FIG. 167) extends axially from a distal end of thefill-finish cartridge 716 for administration. It will be appreciated,however, that a needle insertion mechanism 724 that is disposed at anangle to an axis of the fluid pathway connector 722 and/or drugcontainer 718 could alternately be utilized.

The components of the fluid pathway assembly 720, including the needleinsertion mechanism 724, the fluid pathway connector 722, and the fluidconduit 726 are formed of materials that may be sterilized byconventional sterilization techniques and machinery. The fluid conduit726 may be formed of any appropriate material, for example, a length offlexible tubing, such as plastic tubing. It will be appreciated,however, that fluid pathway connector 722 and the needle insertionmechanism 724 may be directly attached in some embodiments (notillustrated in FIGS. 167 and 168).

The components of the fluid pathway assembly 720 may be sterilized inadvance of such connections, or may be connected prior to sterilizationas a unified component. If sterilized in advance of such connections,the fluid pathway assembly 720 may include an additional seal at thefluid pathway connector 722, such as a permeable seal that may bepierced during assembly or actuation (not illustrated).

The drug container 718 of this and each of the embodiments may be of anyappropriate material and of any appropriate shape and size, and mayinclude a seal to maintain the integrity and sterility of a drugcontained therein. For example, the drug container 718 may be formed ofglass, plastic, or other appropriate material. The drug container 718 ofthis and each of the embodiments may include structure that facilitateshandling, mounting within a drug delivery device, sterilization, and/orinterface with other components of the fill-finish cartridge 716. Forexample, a flange 719 may be provided at any appropriate location alongthe drug container 716. Such a flange 719 may be integrally formed withthe drug container 718 or may be a separate element that is secured tothe drug container. In the illustrated embodiment, the flange 719 is aseparate component that is coupled to a proximal end of the drugcontainer 718.

It will be appreciated that any appropriate drive mechanism may beprovided for moving the medication from the drug container 718 to thefluid pathway assembly 720 in embodiments of the disclosure. Forexample, U.S. application Ser. No. 13/600,114 filed Aug. 30, 2013,discloses an embodiment of a drive mechanism associated with a drugcontainer, and is incorporated herein by reference for everythingdisclosed in that application.

In order to facilitate both filling the drug container 718 andadministering medication from the drug delivery container, the drugcontainer 718 may include openings 718 a, 718 b at the proximal anddistal ends 6127, 728, respectively. In order to seal the drug container718, a permeable seal 150 may be provided at a distal end 728 of thedrug container 718. In this way, once filled, a drug contained withinthe drug container 718 may be maintained in a sterile environment untilsuch time as the seal 150 is pierced by the fluid pathway connector 722to complete the fluid pathway. The permeable seal 150 may be of anyappropriate design and material.

The distal end 728 of the drug container 718 may be assembled with thefluid pathway assembly 720 for sterilization prior to or after fill, aswill be explained in greater detail below. FIG. 168 shows an enlargedcross-sectional view of the fluid pathway connector 722 and thepermeable seal 150 of FIG. 168, after these components are assembled andready for sterilization. While the permeable seal 150 may be a singlethin membrane 762 or the like across the opening 718 b at the distal end728 of the drug container 718, the permeable seal 150 may includefurther structure that facilitates connection with the drug container718 and/or the fluid pathway connector 722. As shown, in at least oneembodiment of the present disclosure, the permeable seal 150 is in theform of a container tip which caps the drug container 718, as well asprovides support for the fluid pathway connector 722. In thisembodiment, the permeable seal 150 may include a portion 152 that restsinside the drug container 718, providing a mating surface to mount thepermeable seal 150 to the drug container 718. To assist in maintainingthe connection of the seal 150 with the drug container 718 a cap 151 maybe provided about portions of the permeable seal 150 and the drugcontainer 718, such as around a lip on the drug container 718. Such acap 151 may be of any appropriate material, such as a foil. While thedrug container 718 necks in at the interface with the permeable seal150, it will be appreciated that alternate designs may likewise beprovided.

The permeable seal 150 may also have an extension 153 which facilitatesmounting with the fluid pathway connector 722. In the embodiment shownin FIG. 168, the fluid pathway connector 722 includes a hub 154 throughwhich a cannula 158 may extend. It will be appreciated by those of skillin the art that, as used herein the term “cannula” 158 includes a needleor a cannula that may be operative to provide the required fluidconnection. The fluid conduit 726 is fluidly connected to the cannula158 as it extends from a surface of the hub 154. The hub 154 of thefluid pathway connector 722 may be employed, as shown here, to mount,attach, or otherwise connect with the extension 153 of the permeableseal 150, the proximal end of the cannula 158 being disposed within abore 760 of the extension 153. Prior to the completion of a fluidpathway between the drug container 718 and the fluid conduit 726, thecannula 158 is held in position as illustrated in FIG. 168.

The permeable seal 150 has a portion that acts as a membrane 762 thatmay be pierced by the cannula 158. In the embodiment of FIGS. 167 and168, the membrane 762 is disposed generally perpendicular to the cannula158 to close off the drug container 718 from the fluid pathway connector722, thereby blocking the fluid pathway from the drug container 718 tothe fluid conduit 726. Upon activation by the patient, a portion of thepermeable seal 150 blocking the drug container 718, here, membrane 762,is caused to be pierced by the cannula 158 of the fluid pathwayconnector 722, thereby completing the fluid pathway and permitting drugfluid to pass from the container 718 to the cannula 158 and the fluidconduit 726, and on to the needle insertion mechanism 724. In order tofacilitate piercing, the extension 153 of the permeable seal 150 may bowoutward in response to sufficient axial pressure, for example, to allowthe cannula 158 to pierce the membrane 762 to complete the fluidpathway.

Accordingly to another aspect of embodiments of the disclosure, the drugcontainer 718, fluid pathway connector 722, and the needle insertionmechanism 724 of the fill-finish cartridge 716 exhibit sufficientstructural integrity to be utilized in a fill-finish process and to beassembled into a housing of a drug delivery device. It will beappreciated that any appropriate fluid pathway connector 722 may beincorporated into embodiments of the disclosure. For example, a mountedfluid pathway connector, such as is disclosed, for example, in U.S.application Ser. No. 13/612,203 filed Sep. 12, 2012, may be utilized.Likewise, an integrated fluid pathway connector, such as is disclosed,for example, in U.S. application Ser. No. 13/796,156 filed Mar. 12,2013, and may be utilized. Both of these applications are incorporatedherein by reference.

Similarly, it will be appreciated that any appropriate connection may beprovided between the fluid pathway connector 722 and the needleinsertion mechanism 724. While examples of some connections aredisclosed in detail herein, it is not the applicant's intention to limitthe disclosure. Such a connection may include, for example, a snapconnection (see FIGS. 210-187), a threaded connection (see FIGS.180-184), an interference connection, a tongue and groove connection, anexternal support (see FIG. 167), or other appropriate connection.

Returning to FIG. 167, In order to provide further structural integrityto such an interface between the fluid pathway connector 722 and thepermeable seal 150, and/or between the fluid pathway connector 722 andthe needle insertion mechanism 724, a carrier 742 may be provided. Thecarrier 742 of this embodiment includes a connection collar 740 and abarrel 6141. For manufacturing purposes, the connection collar 740 mayitself include multiple components, as illustrated in FIG. 167, that maybe coupled together about the fluid pathway connector 722, the permeableseal 150, and a portion of the drug container 718 by any appropriatemechanism. It will be appreciated, however, that a unitary connectioncollar 740 could alternately be provided. It will further be appreciatedthat the connection collar 740 may not be required or desirable in allembodiments, and that such a connection collar 740 may be provided as anintegrated part of the design, or may be fully or partially disposableduring the assembly or sterilization processes.

Further structural integrity may be provided by the barrel 6141, whichmay support the fluid pathway assembly 720 during the sterilization andassembly processes. While any appropriate coupling may be provided, theconnection collar 740 may facilitate coupling of the barrel 6141 aboutthe fluid pathway assembly 720. In the illustrated embodiment, theconnection collar 740 includes a pair of protrusions 744 (only one beingvisible in FIG. 167) that mate with a pair of recesses 746 in the barrel6141. As with the connection collar 740, it will further be appreciatedthat the barrel 6141 may not be required or desirable in allembodiments, and that such a barrel 6141 may be provided as anintegrated part of the design, or may be fully or partially disposableduring the assembly or sterilization processes. In order to permit theneedle insertion mechanism 724 to operate to administer medication, thebarrel 6141 may include an opening 6741 a through which anadministration needle may extend during use.

For operational efficiency, the needle insertion mechanism 724 may becoupled to the fluid pathway connector 722, and the fluid pathwayconnector 722 may be connected to the permeable seal 150 with the needleinsertion mechanism 724 maintained in the non-piercing configurationthrough the sterilization, filling, and assembly processes. In this way,the fill-finish cartridge 716 may appear as shown in FIG. 169, with thefluid pathway assembly 720 residing entirely hidden from the externalenvironment by the carrier 742. Once the drug container 718 is filledwith a pharmaceutical treatment, a seal 764 may be provided in theproximal end 6127 of the drug container 718 to provide a closedfill-finish cartridge 716 that may be inserted into an appropriate drugdelivery device. In the embodiment illustrated in FIGS. 169-170, anelastomeric plunger seal 764 is inserted into the proximal end 6127 ofthe drug container 718. It will be appreciated, however, that otherappropriate sealing arrangement may be provided. In FIGS. 169 and 170,the arrangement of the fluid pathway connector 722, the container 718,and the insertion mechanism 724 relative to each other may be consideredto be a first configuration. The first configuration may facilitate themanufacturing process, for example, by enabling the use of standardfilling equipment and systems. While the first configuration shown inFIGS. 169 and 170 involves the axial alignment of the container 718 andthe insertion mechanism 724, in other embodiments, the firstconfiguration may involve a non-axial alignment of the container 718 andthe insertion mechanism 724, or any other relative positioning of thecontainer 718 and the insertion mechanism 724. Subsequently, whenassembled in the drug delivery device 610, as illustrated in FIG. 165,the fluid pathway connector 722, the container 718, and the insertionmechanism 724 may be arranged relative to each other such they have asecond configuration. The second configuration may involve thenon-alignment of the container 718 and the insertion mechanism 724 asillustrate in FIG. 165, or, in alternative embodiments, the axialalignment of the container 718 and the insertion mechanism 724, or anyother relative positioning of the container 718 and the insertionmechanism 724. In some embodiments, the first configuration is differentfrom the second configuration.

According to another aspect of the disclosure, the fluid pathwayassemblies may be maintained in a sterile condition and the drugcontainers of each assembly may be filled with a pharmaceutical compoundaseptically using processes similar to those known in the art. After apharmaceutical treatment is filled into the drug container and thecontainer is sealed, for example with the plunger seal 764 of theembodiment of FIGS. 167-170, the fill-finish cartridge 716 may beremoved from the sterile filling environment without comprising thesterility or container integrity of the drug container 718, fluidpathway assembly 720, or their individual components.

Alternatively, the fill-finish process may be such that the plunger seal764 is inserted to the proximal end of the drug container 718 prior tofilling the container 718 with a pharmaceutical treatment. In such anembodiment, the pharmaceutical treatment may be filled from the distalend 728 of the drug container 718 prior to insertion and connection ofthe fluid pathway connector 722 and the fluid pathway assembly 720.Accordingly, the fill-finish cartridges of the present disclosure enablethe fluid pathway assemblies of the present disclosure to be filled withpharmaceutical treatments in standard fill-finish processes, greatlyreducing the complexities associated with manufacturing and operation ofthe components and the drug delivery devices in which they areincorporated.

According to another aspect of the disclosure, embodiments of thefill-finish cartridges of the present disclosure may enable the fluidpathways assemblies to be filled in standard fill-finish processes. Inthis regard, the fill-finish cartridges may utilize existing orstandardized fill-finish equipment. A plurality of fill-finishcartridges 716, such as is illustrated in FIGS. 167-170, for example,may be removably mounted, mated, inserted, or otherwise placed into astandard fill-finish tray 770, such as illustrated in FIGS. 171-172, forfilling with pharmaceutical treatments. As explained above, the flange719 of the drug container 718 may assist in placement and handling ofthe fill-finish cartridges 716. The fill-finish tray 770 illustrated inFIGS. 171-172 is configured to hold thirty-six drug containers, here,fill-finish cartridges 716, but trays of any configuration or capable ofholding any number of containers may be utilized.

According to another aspect of the disclosure, fill-finish cartridgesmay be configured to be fixed cartridges or adjustable cartridges. Forexample, the cartridges may have a flexible or adjustable portion thatenables them to bend, rotate, expand, or contract to fit a number ofdifferent fluid pathway assemblies or to mate with fill-finishprocessing trays of different dimensions.

According to yet another aspect of the disclosure, components of someembodiments of the fill-finish cartridges may be incorporated into thedrug delivery devices, while in other embodiments, components of thefill-finish cartridges may be utilized for the fill-finish process andthen discarded upon mounting the fluid pathway assembly and drugcontainer into a drug delivery device. For example, in an embodimentsuch as is illustrated in FIGS. 167-170 is utilized as shown in FIG.165, by removing the barrel, the connection collar may be utilized tomount and/or brace the drug container into position within the drugdelivery device, while the needle insertion mechanism is mountedremotely from and 90.degree. to the drug container.

In the embodiment of FIGS. 173-175, there is illustrated a fill-finishcartridge 816 that includes a carrier 842 that may be disposed of afterthe fill-finish process, that is prior to insertion into a drug deliverydevice. The fill-finish cartridge 816 of this embodiment includes afluid pathway assembly 820 connected to a drug container 818. The fluidpathway assembly 820 includes a needle insertion mechanism 824 coupledto a fluid pathway connector 822 by a fluid conduit 826. A proximal endof the needle insertion mechanism 824 is connected to a distal end of afluid conduit 826, which is connected at its proximal end to the fluidpathway connector 822. In order to provide further support to thefill-finish cartridge 816, the illustrated carrier 842 is disposed aboutportions of the drug container 818 and the fluid pathway assembly 820,that is, the fluid pathway connector 822, the fluid conduit 826, and aportion of the needle insertion mechanism 824.

The carrier 842 is generally an elongated tubular structure that may befabricated in multiple components to facilitate assembly anddisassembly, if desired. In the illustrated embodiment, one portion ofthe carrier 842 includes circumferentially extending arms 843 havingprotrusions 844, while a mating portion of the carrier 842 includesrecesses or openings 846 through which the protrusions 844 may extendwhen assembled about the fill-finish cartridge 816.

In order to assist in maintaining the components of the fill-finishcartridge 816 in their relative positions, the carrier 842 may furtherinclude one or more radially projecting flanges 848 a, 848 b, 848 c. Aswill be apparent from the explanation below, flanges 848 a and 848 b maybe disposed to further secure aspects of the fluid pathway connector 822and the drug container 818 in their relative positions. Further, as willlikewise be apparent from the explanation below, flanges 848 b and 848 cmay be disposed to maintain the fill-finish cartridge 816 in anun-actuated position during filling, and, optionally, placement within adrug delivery device. In order to permit actuation of the device, thecarrier 842 may be removed from the fill-finish cartridge 816 anddiscarded. The carrier 842 may further include a removable brace 840.The removable brace 840 may have a generally U-shaped structure andsurfaces that confront the surfaces of the fill-finish cartridge 816 toprevent premature completion of the fluid pathway from the drugcontainer 818 to the fluid pathway connector 822. The removable brace840 may remain with the fill-finish cartridge 816 as it is assembledinto a housing of a drug delivery device; in some embodiments, structurewithin the housing of the drug delivery device may confront one or moresurfaces of the removable brace 840 to cause the removable brace 840 todisengage from the fill-finish cartridge 816 as it is assembled into thehousing.

The drug container 818 is an elongated, generally annular structure,although the drug container 818 may be of an alternate design. Forexample, a flange 819 may be provided at any appropriate location alongthe drug container 818. Such a flange 819 may be integrally formed withthe drug container 818 or may be a separate element that is secured tothe drug container 818. In the illustrated embodiment, the flange 819 isa separate component that is coupled to a proximal end 827 of the drugcontainer 818. In an embodiment, the flange 819 may interface with awall of a housing of a drug delivery device incorporating thefill-finish cartridge 816. Further, in this embodiment, a flange 817 isprovided at the distal end 828 of the drug container 818. As illustratedin FIG. 175, the flange 817 may engage with flange 848 a of the carrier842 to facilitate the maintenance of the relative positions of thecomponents of the fill-finish cartridge 816 during the fill-finishprocess and handling.

In order to seal the drug container 818, a permeable seal 850 may beprovided at the distal end 828 of the drug container 818. In this way, adrug contained within the drug container 818 may be maintained in asterile environment until such time as the seal 850 is pierced by thefluid pathway connector 822 to complete the fluid pathway. The drugcontainer 818 may be assembled with the permeable seal 850 and the fluidpathway assembly 820 for sterilization prior to or after fill. Thepermeable seal 850 may be of any appropriate design and material. Thepermeable seal 850 includes a thin membrane 862 or the like that may bepierced in order to complete the fluid pathway from the drug container818 through the fluid pathway connector 822 and fluid conduit 826 to theneedle insertion assembly 824.

The permeable seal 850 may include structure that facilitates connectionwith the drug container 818 and/or the fluid pathway connector 822. Forexample, the permeable seal 850 may include a portion 852 that restsinside the drug container 818, providing a mating surface to mount thepermeable seal 850 to the drug container 818.

The fluid pathway connector 822 maybe of any appropriate design. Suchpiercing arrangements are disclosed, for example, in U.S. applicationSer. No. 13/612,203, and in U.S. application Ser. No. 13/796,156, bothof which are incorporated herein by reference.

Referring to FIG. 175, the illustrated fluid pathway connector 822includes a cannula 858 that is disposed to pierce the membrane 862 ofthe permeable seal 850 during actuation, the cannula 858 being spacedfrom the permeable seal 850 in the un-actuated position (see FIG. 175),and progressing respectively axially in a proximal direction to confrontand pierce the membrane 862 as a result of actuation. In the embodimentshown in FIG. 175, the fluid pathway connector 822 includes a hub 854through which the cannula 858 extends. A pathway from the cannula 858secured within the hub 854 extends from the lumen of the cannula 858 toa lumen of the fluid conduit 826. Accordingly, when the cannula 858pierces the membrane 862 of the permeable seal 850, the fluid pathway isprovided between the drug container 818, the fluid conduit 826 and theneedle 825 of the needle insertion mechanism 824.

In order to maintain the hub 854 and, therefore, the cannula 858 in adesired position relative to the permeable seal 850 closing the drugcontainer 818, the fluid pathway connector 822 further includes a boot853 formed of collapsible material, such as an elastomeric material. Adistal end of the boot 853 includes a generally axially extending bore853 a that is disposed about a portion of the hub 854, while a proximalend of the boot 853 includes a generally radially extending flange 853b. The permeable seal 850 may also include a flange 849 that may besandwiched between the flange 853 b of the boot 853 of the fluid pathwayconnector 822 and the flange 817 at the distal end 828 of the drugcontainer 818. As with the embodiment illustrated in FIGS. 167-170, aretaining structure, such as a cap 851 may be provided about theperiphery of the flanges 817, 849, 853 b.

The fluid pathway connector 822 of the fill-finish cartridge 816 may becaused to pierce the membrane 862 of the permeable seal 850 to completethe fluid pathway, for example, by manual depression of the proximal end827 of the drug container 818 or by an alternate arrangement. Duringactuation, the boot 853 bows outward to allow relative axial movementbetween the hub 854 and the permeable seal 850 such that the cannula 858pierces the membrane 862 of the permeable seal 850 to fluidly connectthe drug container 818 to the delivery needle 825 of the needleinsertion mechanism 824 via the fluid conduit 826.

In order to inhibit inadvertent activation of the fluid pathwayconnector 822 once the carrier 842 is removed, the removable brace 840may be provided about a portion of the circumference of the sterile boot853 and/or between surfaces that inhibit axial movement of the hub 854relative to the drug container 818. The removable brace 840 may be arelatively rigid structure that confronts opposing surfaces 840 a, 840b, for example, on a surface of the hub 854, and the flange 853 b of thesterile boot 853 or, as here the cap 851 along the flange 853 b; as aresult, the removable brace 840 inhibits axial movement of hub 854relative to the seal 850. The removable brace 840 illustrated alsoclosely follows at least a portion of the periphery of the sterile boot853; as a result, the removable brace 840 likewise prevents the sterileboot 853 from bowing outward as the cannula 858 moves axially to piercethe seal 850. In this embodiment, the removable brace 840 may be slidout of position on the sterile boot 853 by the patient prior toassembling the fill-finish cartridge 816 into the drug delivery deviceor by the action of placement into the drug delivery device, forexample, as the removable brace 840 engages confronting surfaces of thehousing of the delivery device (not illustrated).

The needle insertion mechanism 824 may be of any appropriate design. Theneedle insertion mechanism 824 illustrated in connection with theembodiment of FIGS. 173-176 likewise includes a needle retractionmechanism, and is shown and explained in greater detail in U.S.application Ser. No. 13/599,727, which is incorporated by reference.

The insertion mechanism 824 includes an insertion mechanism housing 865having one or more lockout windows 865 a, a base 866, and a sterile boot879. The base 866 includes an opening to passage of the needle 825 andmay include a sealing membrane 867 that, at least in one embodiment, isremovable prior to use of the fill-finish cartridge 816. Alternatively,the sealing membrane 867 may remain attached to the bottom of the base866 such that the needle 825 pierces the sealing membrane 867 duringoperation of the fill-finish cartridge 816 within the drug deliverydevice incorporating the same.

The insertion mechanism 824 may further include an insertion biasingmember 868, a hub 869, a needle 825, a refraction biasing member 871, aclip 872, a manifold guide 873, a septum 874, a cannula 875, and amanifold 876. As illustrated in FIG. 175, both the insertion andretraction biasing members 868, 871 are held in energized states. Themanifold 876 may connect to sterile fluid conduit 826 to permit fluidflow through the manifold 876, cannula 875, and into the body of thepatient during drug delivery, as will be described in further detailherein.

As used herein, “needle” is intended to refer to a variety of needlesincluding but not limited to conventional hollow needles, such as arigid hollow steel needles, and solid core needles often referred to as“trocars”. In an embodiment, the needle 825 may be a 27 gauge solid coretrocar and in other embodiments, the needle may be any size needlesuitable to insert the cannula for the type of drug and drugadministration (e.g., subcutaneous, intramuscular, intradermal, etc.)intended.

Upon assembly, the proximal end of needle 825 is maintained in fixedcontact with hub 869. The needle 825 may be positioned to move through acannula 875, if provided, in order to further control movement of theneedle 825. The hub 869, and therefore the needle 825, is maintained inselective contact with the manifold guide 873 by the clip 872. Whilebiasing members 868 and 871 bear on the manifold guide 873, the manifoldguide 873 is maintained in position by at least one lockout pin 878,which extends through window 865 a of the housing 865.

Actuation of the needle insertion 824 device results from removal of thelockout pin 878. The lockout pin 878 may be removed from the window 865a either directly or indirectly as a result of actuation of thefill-finish cartridge 816. Upon removal of the lockout pin 878, themanifold guide 873 carrying the hub 869 and needle 825 is permitted tomove axially under the biasing force of the injection biasing member868. That is, the needle 825 moves into the injection position. As thehub 869 and needle 825 move to the injection position, the sterile boot879 collapses.

In at least some embodiments, such as the embodiment shown in FIG. 175,the needle insertion mechanism 824 further includes a refractionmechanism that retracts the needle 825 following injection. Such aretraction mechanism may be of any appropriate design. As the manifoldguide 873 moves axially in the distal direction, the clip 872 releasesthe hub 869. Upon release, the biasing force of the retraction biasingmember 871 causes hub 869 and the associated needle 825 to retract.

As with the embodiment of FIGS. 167-170, the needle insertion mechanism824 of FIGS. 173-176 includes an axially aligned structure, such thatthe administration needle 825 extends axially from a distal end of thefill-finish cartridge 816 during administration. It will be appreciatedthat the components may be secured together by any appropriate structureand method. The relative positions of the fluid pathway connector 822and the needle insertion mechanism 824 may be maintained by, forexample, a bracket 880, as may be seen in FIGS. 174-176. The illustratedbracket 880 extends between the hub 854 of the fluid pathway connector822 and the insertion mechanism housing 865, as may best be seen in FIG.175. The bracket 880 may perform additional functions such as, forexample, management of the fluid conduit 826.

It will be appreciated that in some embodiments wherein the bracket 880is removed from its connection with either of the fluid pathwayconnector 822 or the needle insertion mechanism 824, or wherein thefill-finish cartridge does not include the bracket 880, the fluidconduit 826 may provide a flexible fluid connection between the fluidpathway connector 822 and the needle insertion mechanism 824, allowingthe needle insertion mechanism 824 and the fluid pathway connector 822to be placed other than in axial alignment. Such embodiments areillustrated, for example, in FIG. 165 or FIGS. 177-180.

Referring to FIG. 177, there is illustrated another embodiment of a drugdelivery device 910 according to teachings of the disclosure. A portionof the housing 912 of the drug delivery device 910 is broken away inorder to illustrate the relative positions of the components containedtherein. The fill-finish cartridge 916 includes a drug container 918 towhich a fluid pathway assembly 920 is coupled. The fluid pathwayassembly 920 includes a fluid pathway connector 922, fluidly coupled toa needle insertion mechanism 924 by a fluid conduit 926. It will beappreciated that, in this embodiment, while they remain fluidly coupled,the needle insertion mechanism 924 is decoupled from the fluid pathwayconnector 922 of the fill-finish cartridge 916 when assembled into thehousing 912. As shown in FIGS. 178 and 179, during the fill-finishprocess, the components are aligned to allow the fill-finish cartridge916 to be readily placed in a tray, such as are illustrated in FIGS. 171and 172. It is noted, however, that the components are not in axialalignment in the fill-finish cartridge 916 during the fill-finishprocess inasmuch as the axis of the needle insertion mechanism 924extends perpendicular to the axis of the drug container 918 and fluidpath connection 922. As may be best seen in FIG. 178, the needleinsertion mechanism 924 may include a sealing membrane 967 that, atleast in one embodiment, is removable prior to use of the fill-finishcartridge 916 within the drug delivery device to allow passage of aneedle from the needle insertion mechanism 924. Alternatively, thesealing membrane 967 may remain attached to the bottom of the needleinsertion mechanism 924 such that the needle pierces the sealingmembrane 967 during operation of the fill-finish cartridge 916 withinthe drug delivery device 910 incorporating the same.

Referring to FIG. 178, there is illustrated the fill-finish cartridge916 along with a carrier 942 that partially surrounds the assembledfill-finish cartridge 916 during the fill-finish process. As may be seenin FIG. 178, the carrier 942 substantially surrounds a distal portion ofthe drug container 918, the fluid pathway connector 922, and the needleinsertion mechanism 924. The carrier 942 of this embodiment includesthree separate sections, although a greater or lesser number may beprovided. In this embodiment, a portion of the carrier 942 is disposableprior to placement of the fill-finish cartridge 916 into the housing 912of the drug delivery device 910, while a portion remains on thefill-finish cartridge 916 when disposed in the housing 912, and may beutilized in operation of the device 910.

As may be seen in FIGS. 178 and 179, the carrier 942 includes a firstbarrel section 941 a and a second barrel section 941 b. The first andsecond barrel sections 941 a, 941 b may be selectively coupled togetherby any appropriate mechanism. In the illustrated embodiment, a couplingarrangement similar to that illustrated in FIGS. 173-75 is utilized suchthat the first and second sections 941 a, 941 b may be decoupled andremoved prior to placement into the housing 912 of the drug deliverydevice 910. The carrier 942 further includes a collar 940 that, whenassembled to the fill-finish cartridge 916, completes the barrel.

The fluid pathway connector 922 and the needle insertion mechanism 924may be of any appropriate design. The illustrated fluid pathwayconnector 922, for example, is as explained with regard to FIGS.173-176, and the needle insertion mechanism 924 may likewise be asdescribed with regard to FIGS. 173-176. Referring to FIG. 179, in short,a permeable seal 950 is disposed between the drug container 918 and asterile boot 953 of the fluid pathway connector 922. A cannula 958extending from a hub 954 is axially disposed within the sterile boot953. Continued relative axial, proximal movement of the cannula 958toward the permeable seal 950 results in a piercing of the permeableseal 950, and completion of the fluid pathway to the needle insertionmechanism 924.

In assembly of the filled fill-finish cartridge 916 into the drugdelivery device housing 912, the collar 940 remains coupled to the fluidpathway connector 922, as illustrated in FIG. 177. In some embodimentsof the disclosure, the carrier, or a portion of the same such as thecollar 940 here, may be utilized in the operation or actuation of thefill-finish cartridge 916. In this embodiment, an activation mechanism914, such as a button, may be provided along an outer surface of thedrug delivery device housing 912 in order to permit the patient toselectively provide medication. In this embodiment, the activationmechanism 914 asserts an axial, proximally directed force on the collar940. The collar 940 further asserts an axial, proximally directed forceon the hub 954, causing the cannula 958 to pierce the permeable seal 950of the fluid pathway connector 922 to complete the fluid pathway fromthe drug container 918 to the needle insertion mechanism 924. The needleinsertion mechanism 924 may be actuated by any appropriate operation.For example, the movement of a portion of the collar 940 may cause thedislodgement of the lockout pin, causing actuation of the needleinsertion mechanism 924, as explained in greater detail with regard tothe embodiment illustrated in FIGS. 173-176.

Turning now to the embodiment of FIGS. 180-186, the fill-finishcartridge 1116 includes a drug container 1118 having proximal and distalends 1127, 1128. The proximal end 1127 may include a flange 1119 and isadapted to receive a plug or plunger seal 1164, while the distal end1128 may include a flange 1117 and is adapted to receive a permeableseal 1150 in conjunction with a fluid pathway assembly 1120. The fluidpathway assembly 1120 includes a fluid pathway connector 1122 and aneedle insertion mechanism 824 fluidly coupled by a fluid conduit 1126.

In this embodiment, the fluid pathway connector 1122 is integrated withthe permeable seal of the drug container 1118. The fluid pathwayconnector 1122 may best be seen in the cross-sectional view of FIG. 181and the exploded view of FIG. 183. The fluid pathway connector 1122includes a hub assembly 1156 having a hub 1154 and a cap 1155. A cannula1158 is secured to the hub 1154 to provide a fluid path therethrough.The fluid conduit 1126 may be coupled to the cannula 1158 by anyappropriate structure. In this embodiment, the fluid conduit 1126 iscoupled to a nipple 1159 that is fluidly open to the cannula 1158.

In order to maintain the hub assembly 1156 along with the associatedcannula 1158 in position relative to the permeable seal 1150, a sealmount 1130 is provided. While the seal mount 1130 may be coupled to thepermeable seal 1150 by any appropriate structure, in the illustratedembodiment, the permeable seal 1150 and the seal mount 1130 includemating structure in the form of respective interlocking flanges 1131,1132.

While the hub assembly 1156 may be assembled with the seal mount 1130and permeable seal 1150 for coupling to the drug container 1118, thepermeable seal 1150 and seal mount 1130 are slidably disposed relativeto the hub assembly 1156. In order to allow this sliding, yet coupledrelationship, the hub 1154 includes one or more resilient posts 1154 athat present surfaces that interlock with a complimentarily disposedbore 1160 in the seal mount 1130. As shown in FIG. 181, the whenassembled together, the cannula 1158 is disposed subjacent the membrane1162 of the permeable seal 1150. In this way, the permeable seal 1150,the seal mount 1130 and the coupled hub assembly 1156 form an integratedfluid pathway connector 1122 that may be assembled into the distal end1128 of the container 1118.

In order to further facilitate assembly of the fluid pathway connector1122 to the container 1118, a cap 1151 may be provided. One or moregaskets 1133 may be provided between adjacent surfaces of the fluidpathway connector 1122 and, for example, the flange 1117 of the drugcontainer 1118. One such gasket 1133 is illustrated in FIG. 181,although additional gaskets may be provided.

The needle insertion mechanism 1124 may be of any appropriate design,such as, for example, the needle insertion mechanism 1124 illustrated inFIG. 175. The cannula 1158 of the fluid pathway connector 1122 isfluidly connected to the needle 425 of the needle insertion mechanism1124 by way of the fluid conduit 1126.

In this embodiment the fluid pathway connector 1122 and the needleinsertion mechanism 1124 are coupled, for example by mechanicalcoupling, by way of complimentary threads 1134, 1135. In the illustratedembodiment, fluid pathway connector 1122, here, the hub 1154, includesexternal threads 1134, while the needle insertion mechanism 1124, here,a bore 436 of an extension 1137 of the insertion mechanism housing 1165,includes complimentary internal threads 1135. It will be appreciatedthat alternate arrangements are envisioned. For example, the threadingarrangement could be reversed, the fluid pathway connector 1122including internal threads and the needle insertion mechanism 1124including external threads. Alternately, a threaded collar, or the like,could be provided to couple the components together.

Moreover, although the fluid pathway connector 1122 and the needleinsertion mechanism 1124 are coupled in axial alignment in thefill-finish cartridge 1116 for the fill process, the components could bealternately disposed. For example, the axis of the needle insertionmechanism 1124 could be disposed at a right angle to the axis of thefluid pathway connector 1122 and the drug container 1118.

According to another aspect of the disclosure, the fill-finish cartridge1116 provides controlled management of the fluid conduit 1126. In thisembodiment, the threaded coupling of the needle insertion mechanism 1124and the fluid pathway connector 1122 may provide controlled placement ofthe fluid conduit 1126. The uncoupled needle insertion mechanism 1124and fluid pathway connector 1122 are illustrated in FIG. 184. As theneedle insertion mechanism 1124 and the fluid pathway connector 1122 arethreaded together to the positions illustrated in FIGS. 180 and 181, thefluid conduit 1126 winds about the housing 1165 of the needle insertionmechanism 1124. While the needle insertion mechanism 1124 and the fluidpathway connector 1122 are illustrated in a disassembled configurationwith the fluid pathway connector 1122 being assembled to the container1118 in FIG. 184, it will be appreciated that the components may beassembled in any order. For example, the needle insertion mechanism 1124and the fluid pathway connector 1122 may be assembled together prior tocoupling the fluid pathway connector 1122 to the container 1118 to formthe fill-finish cartridge 1116.

Turning to the embodiment illustrated in FIGS. 185-187, the fill-finishcartridge 1216 illustrated is similar in operation to the fill-finishcartridge 1116 of FIGS. 180-184. The fill-finish cartridge 1216 of FIGS.185-187 differs, however, in that the fluid pathway connector 1222 iscoupled to the needle insertion mechanism 1224 by way of a snapconnection 1238, the needle insertion mechanism 1224 and the fluidpathway connector 1222 including complementary structure that allow thecomponents to snap together. For example, the housing 1265 of the needleinsertion mechanism 1224 may include an extension 1237 having a recessor bore 1236, or female portion, adapted to receive a corresponding maleportion 1234 of the fluid pathway connector 1222. In order to ensureaxial alignment of the extension 1237 and male portion 1234, each maypresent one or more confronting shoulders. For example, the recess 1236of the may include shoulders 1282, 1284 against which one or moreoutwardly extending shoulders 1283, 1285 of the fluid pathway connector1222 seat. To facilitate connection, the hub 1254 of the fluid pathwayconnector 1222 may include one or more resilient fingers 586 extendingfrom the hub 1254. During assembly, the fingers 586 may flex such thatthe shoulders 1283 may move generally radially inward as the fingers 586are moved through the recess or bore 1236, and snap outward intoengagement with shoulders 1282 when the fluid pathway connector 1222 andthe needle insertion mechanism 1224 are in their final assembled axialpositions. It will be appreciated, however, that the snap connection1238 may have alternate structure as, for example if the fluid pathwayconnector 1222 included a shouldered recess and the needle insertionmechanism 1224 included mating outwardly extending shoulders.

As with the embodiment of FIGS. 180-184, the embodiment of FIGS. 185-187allows for controlled management of fluid conduit 1226 fluidlyconnecting the fluid pathway connector 1222 and the needle insertionmechanism 1224. For example, the conduit may be wound around theperiphery of the housing 1265 of needle insertion mechanism 1224, asillustrated in FIG. 187, before, after, or during the engagement of thesnap connection 1238.

While a threaded connection has been described with regard to FIGS.180-184, and a snap connection with regard to FIGS. 185-187, it will beappreciated that alternate mechanical connections may be utilized toprovide sufficient structural integrity to the cartridge to facilitatefilling the container in a conventional fill-finish process. Forexample, a tongue and groove type connection may be utilized.Alternately, or additionally, an external support, such as the bracket880 of FIGS. 173-176 may be utilized, or the relative positions may bemaintained by way of a carrier, such as the carrier 742 of FIGS.167-170. Other mechanical coupling arrangements are likewise within thepurview of the disclosure.

It will thus be appreciated that the inventive arrangement describedherein provide varied designs of components that may be assembled invarious configurations to provide various designs of fill-finishcartridges that may be sterilized and filled in conventional fill finishprocesses.

As a further benefit, because the embodiments of the present disclosureenable the manufacture of pre-filled infusion or injection pumps, thesepumps may be configured to be single-use or reusable pumps. For example,the fluid pathway assemblies and/or fill-finish cartridge of the presentdisclosure may be configured to be cartridges which can be replacedwithin reusable pump devices.

Some embodiments of the present disclosure enable the drug container tobe filled in a standard fill-finish process, without the need to exposethe drug treatment to the sterilization environment or conditions. Somedrug treatments, however, are capable of withstanding the sterilizationconditions without degrading, losing efficacy, or the like. Accordingly,in at least one embodiment of the present disclosure, sterilization ofthe fluid pathway assembly and/or the fill-finish cartridge may occurafter the components have been assembled and the drug container has beenfilled with a pharmaceutical treatment. This method of manufacturing,filling, and using the novel embodiments of the present disclosure stillmay provide the benefit of being adaptable to a standard fill-finishprocess. Additionally, this method enables drug delivery devicemanufacturers and fillers the benefit of only needing to sterilize thecomponents of the fluid pathway (i.e., components which may come incontact with the drug fluid). The fill-finish cartridges, fluid pathwayassemblies, and individual components of the present disclosure may besterilized prior to their integration in a drug delivery device. Assuch, the other components of the drug delivery device which generallynever contact the drug fluid do not need to be sterilized because of theadvantages offered by the present disclosure. Accordingly, theembodiments of the present disclosure enable more complex geometries andmore standard materials, for example, to be employed for the manufactureof advanced drug delivery devices.

The novel configurations of the fluid pathway assemblies and thefill-finish cartridges of the present disclosure may provide substantialbenefits in the marketplace. Embodiments of the present disclosure canreadily be manufactured in a sterile environment, integrated intostandard drug filling (e.g., fill-finish) process lines for asepticfilling of pharmaceutical treatments, and utilized for cost-effectiveassembly into drug delivery devices. Each of these advantages hassubstantial benefits over existing methodologies.

For example, because the fluid pathway assemblies themselves can besterilized and maintained in a sterile condition during the filling anddevice assembly processes, the resulting drug delivery device does notneed to be sterilized after assembly (i.e., terminally sterilized). Thisavoids a number of known challenges faced by existing methodologies forthe manufacture of drug delivery devices.

Conventional drug delivery devices often require filling at time-of-usebecause the terminal sterilization of the device cannot be completedwith the pharmaceutical drug within the drug container. Variouspharmaceutical drugs cannot withstand the temperatures, pressures, andother conditions necessary for sterilization of the device afterassembly. In other words, because existing manufacturing processesrequire sterilization of the entire device, the drug cannot be“pre-filled” into the device prior to sterilization. This adds a complexstep after final assembly of the device, which often requires costlyadditional equipment, handling of separate drug containers, and/ortraining of the patient to perform the filling step themselves prior toinjection. Instead, the embodiments of the present disclosure enable themanufacture, assembly, and use of pre-filled drug delivery devices whichmaintain the sterility of the fluid pathway assembly through the variousmanufacturing steps.

Additionally, because the drug delivery devices which incorporate thenovel embodiments of the present disclosure do not need to be terminallysterilized, the components of the devices may comprise of other, oftenless expensive, materials which would not normally withstand thesterilization environment. For example, less expensive plastics may beutilized for certain device components because they do not need to besterilized after assembly.

In other words, the embodiments of the present disclosure may allow themanufacturer to sterilize only the components which will be in contactwith the drug fluid and/or which are necessary to maintain sterile fluidpathways. These embodiments may also allow the pharmaceutical filler tomaintain the sterility of these components during the filling andfinishing steps associated with the assembly of the drug deliverydevices. Similarly, drug delivery devices which incorporate the fluidpathway assemblies of the present disclosure may have smaller or moreefficient geometries as the device does not have to be configured forsterilization after assembly.

Additionally, the embodiments of the present disclosure allow for theutilization of standard fill-finish processes to fill the drugcontainer. This greatly simplifies the manufacturing processes used tobuild drug delivery devices. Standard fill-finish processes utilizetrays which hold multiple drug containers, such as syringes. Theembodiments of the present disclosure enable a drug delivery devicemanufacturer, pharmaceutical company, or contract drug filler to fillthe drug containers for infusion or injection pumps using the samestandard fill-finish processes. These drug containers can be filledaseptically, as is common industry practice, in a cost-efficient mannerthat preserves the sterility of the fluid pathway assembly. Aftermounting of the fluid pathway connector mechanism, the combined assemblycan then be mated into a drug delivery device without requiring theremainder of the device components to be sterilized. Accordingly,embodiments of the present disclosure may provide novel components whichenable the fluid pathway assemblies to be sterilized, assembled,filling, and incorporated into drug delivery devices in a cost-efficientand streamlined process.

Additionally, the fluid pathway assemblies of the present disclosureutilize materials that are substantially non-reactive with therapeuticfluids or drugs, and are suitable for use in pharmaceutical gradeapplications. The novel fluid pathway assemblies and fill-finishcartridges are configured to minimize or eliminate the possibility ofcontact or interaction between degradable materials, such as certainplastics, with the therapeutic fluids or drugs. The fluid pathwayassemblies, with adaptable needle injection and retraction mechanisms,also may provide fluid conduits from the drug container to the patient,through the needle or cannula, which are substantially absent ofdegradable materials. Such configurations, when integrated into thefill-finish cartridges or drug delivery devices, may provide increasedstability and shelf-life parameters to the drug and drug deliverydevices. These characteristics are thought to be highly desirable forgenerally all pharmaceutical treatments, but perhaps especially of valuein drug delivery devices for use with biologics and other complextherapies.

One or more embodiments of the present disclosure may further includecertain standard components. For example, the fill-finish cartridgeconfigurations and drug delivery devices of the present disclosure mayinclude one or more membranes. In at least one embodiment, one or morepermeable membranes are employed to seal the drug container and/or toensure a sterile environment and container integrity within the drugchamber. Similarly, the drug container may include a flange. The flangemay be pre-formed along any portion of the container, or may be aseparate component that is connected to or affixed to the container. Inat least one embodiment, the flange is a removable connected componentthat is connected at the proximal end of the drug container. The flangemay be configured to allow the fill-finish cartridge and drug containerto rest within a fill-finish tray, for filling with a pharmaceuticalcompound within a standard fill-finish process. The position, shape,number, and materials for such components may vary, as would be readilyappreciated by a skilled artisan, to meet any number of desiredcharacteristics.

Similarly, while the components of the fill-finish cartridge and thefluid pathway assembly are described herein as separate components, itis within the contemplation of the present disclosure that certaingroups of these components may be combined to form a single componentcapable of performing the functions of the individual components. In atleast one embodiment the needle insertion and needle retractionmechanisms may be one unified component that may provide a dualfunction. Additionally, as would be appreciated by one having ordinaryskill in the art, the components of the devices may be manufactured asindividual components or as single components. For example, the flangemay be a component that is pre-formed, during the manufacturing process,as a part of the drug container itself. Accordingly, in at least oneembodiment, the flange may be a glass flange extension of the container.Furthermore, while the components of the fill-finish cartridge and fluidpathway assembly are described herein as separate components, they maybe unified components having multiple functions. The configuration ofthe components and their assembly may vary based on the assemblyprocess, the device parameters, and other desired characteristics.

Embodiments of the present disclosure may provide fluid pathwayassemblies, fill-finish cartridges, methods of manufacturing suchcartridges, and their methods of use. The fill-finish cartridges andfluid pathway assemblies may be utilized in a number of differentconfigurations and may themselves comprise of one or more components.Such modifications are contemplated by and encompassed in theembodiments of the present disclosure. Other components may similarly besingle components, unified components, or multi-purpose components, asdescribed in the embodiments discussed above. Thus, it is intended thatthe present disclosure covers the modifications and variations of thisdisclosure, provided they come within the scope of the appended claimsand their equivalents.

XXII. Temperature Control System

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-187 may be configured to incorporate the embodiments of thetemperature control system described below in connection with FIG. 188,where appropriate.

For some drugs, temperature is an important consideration both duringand prior to patient delivery. Biologic drugs, for example, oftentimesrequire refrigeration or frozen storage prior to patient delivery. Whilecold temperatures may help extend the shelf life of the drug, they canresult in an increased viscosity of the drug. A more viscous drug maytake longer to inject and/or require additional injection force.Furthermore, injecting a cold drug can be uncomfortable, and potentiallyeven painful, for some patients. Therefore, a drug which has been storedin a cold state usually is allowed to warm to near room temperatureprior to patient delivery. This warming up period can take upwards of 30minutes, which can be inconvenient to the patient and consequently havean adverse impact on patient compliance rates.

The drug delivery devices of the present disclosure can be configured toinclude a temperature control system for monitoring and/or controllingthe temperature of the drug within the device. One embodiment of a drugdelivery device, denoted by reference numeral 11010, incorporating atemperature control system 11600 according to principles of the presentdisclosure is illustrated by FIG. 188. While the temperature controlsystem 11600 is described in conjunction with particular elements andfeatures of the drug delivery device 11010, the temperature controlsystem 11600 can be implemented, where appropriate, in any one of thedrug delivery devices disclosed herein, including, but not limited to,any one of the drug delivery devices 10, 910, 6010, 8000, 9010, 9210,9310, 9410, 9510, 9610, 11600, 12340, 12710, 11010, 13100, 19010, or19020. Various elements of the drug delivery device 11010 are similar instructure and/or function to those previously described in connectionwith the drug delivery device 10. These elements are assigned referencenumbers similar to those previously provided with the addition of thetwo-digit prefix “11,” and, for the sake of brevity, are not describedin detail below. For example, the drug delivery device 11010 includes aneedle insertion mechanism 11200 which bears at least some similaritiesin structure and/or function to the needle insertion mechanism 200 ofthe drug delivery device 10. It should be noted, however, that thetemperature control system 11600 is not limited to being used inconjunction with elements of the drug delivery device 10, and can beimplemented in any one of the drug delivery devices disclosed herein,where appropriate.

Turning to FIG. 188, the drug delivery device 11600 may include a startbutton 11014, a drug container 11050, a drive mechanism 11100, a needleinsertion mechanism 11200, a fluid pathway connector 11300, a power andcontrol system 11400, and a temperature control system 11600. The drugcontainer 11050 may include a barrel 11058 and a plunger seal 11060moveable through the barrel 11058 to discharge a drug from the barrel11058, and a pierceable seal (not illustrated) controlling access to aninterior of the barrel 11058. The drive mechanism 11100 may include adrive housing 11130, a piston 11110 moveable relative to the drivehousing 11130 and configured to impart movement to the plunger seal11060, and a piston biasing member 11106 disposed between the drivehousing 11130 and the piston 11110. The fluid pathway connector 11300may define a sterile fluid flowpath between the drug container 11050 andthe insertion mechanism 11200. The fluid pathway connector 11300 mayinclude a connection hub 11310, a tubular conduit 11030 providing fluidcommunication between the connection hub 11310 and the insertionmechanism 11200, and a piercing member (not illustrated) configured topierce the pierceable seal to establish fluid communication between thebetween the barrel 11058 and the tubular conduit 11030 during drugdelivery.

The tubular conduit 11030 may include a first flexible tube 11032, asecond flexible tube 11034, and a rigid tube 11036 connected andproviding fluid communication between the first and second flexibletubes 11032 and 11034. The first flexible tube 11032 may fluidly connectthe connection hub 11310 with a proximal end 11037 of the rigid tube11036, and the second flexible tube 11032 may fluidly connect the needleinsertion mechanism 11200 with a distal end 11038 of the rigid tube11036. The first and second flexible tubes 11032 and 11034 each may bemade of a material that is more flexible than the material used toconstruct the rigid tube 11036. In at least one embodiment, the firstand second flexible tubes 11032, 11034 are made of a polymeric material,and the rigid tube 11036 is made of metal. As described below, thematerial used to construct the rigid tube 11036 may possess a relativelyhigh thermal conductivity such that heat can be transferred from aheating element to a drug flowing through the rigid tube 11036 duringdelivery.

An inner diameter of the rigid tube 11036 may be less than an innerdiameter of the first flexible tube 11032 and/or the second flexibletube 11034. Accordingly, the rigid tube 11036 may serve as a flowrestrictor that reduces and/or regulates the flow rate of the drugduring delivery. The rigid tube 11036 may be replaced with other rigidtubes having different inner diameters depending on the target flowrate. Furthermore, the inclusion of a flow restrictor may providebroadened design space when coupled with other contributing elementssuch as a drive spring. In an alternative embodiment, the rigid tube11036 may have an inner diameter that is equal to that of the firstflexible tube 11032 and/or the second flexible tube 11034.

Still referring to FIG. 188, the temperature control system 11600 mayinclude a heating element 11602, a first temperature sensor 11604, and asecond temperature sensor 11606. In the illustrated embodiment, theheating element 11602 includes an electrically-conductive coil that iswrapped around and contacts an exterior of the rigid tube 10036. Theheating element 11602 may be electrically connected to the power andcontrol system 11400, such that the heating element 11602 is suppliedwith electricity from the power and control system 11400 in a controlledmanner. The impedance of the material used to construct the heatingelement 11602 may cause the heating element 11602 to convert at leastsome of the electricity it is supplied with into heat. Due to thecontact or close proximity of the heating element 11602 to the rigidtube 11036, the heat generated by the heating element 11602 may warm therigid tube 11036, and due to the thermal conductivity of the rigid tube11036, warm a drug flowing through the rigid tube 11036.

The inclusion of the heating element 11602 may eliminate the need for apre-delivery warming period in the case where the drug delivery device11010 has been removed from cold storage. Furthermore, heat transferfrom the heating element 11602 to the drug may be relatively efficient,because the volume of drug per unit length of the rigid tube 11036 isrelatively small. Therefore, it may be possible to warm the drug to atarget temperature without reducing the flow rate or increasing thelength of the flow path. Accordingly, it may be possible to heat thedrug during delivery without altering the duration of delivery.Moreover, the heating element 11602 can be installed with little or nomodifications to a pre-existing fluid pathway connector, therebyreducing manufacturing and/or design costs.

In some embodiments, the heating element 11602 may be dynamicallycontrolled based on real-time drug temperature measurements to ensurethat the drug is delivered to the patient at a desired temperature. Asshown in FIG. 77, the first temperature sensor 11604 may be connected tothe proximal end 11037 of the rigid tube 11036 so that the firsttemperature sensor 11604 can measure the temperature of the drug flowinginto the rigid tube 11036. The second temperature sensor 11606 may beconnected to the distal end 11038 of the rigid tube 11036 so that thesecond temperature sensor 11606 can measure the temperature of the drugflowing out of the rigid tube 11036. In some embodiments, the first andsecond temperature sensors 11604 and 11606 may not directly measure thetemperature of the drug. Rather, the first and second temperaturessensors 11604 and 11060 may measure the temperature of, respectively,the inlet and outlet portions of the rigid tube 11036 (or other portionsof the drug delivery device proximate to the drug). These temperaturesmeasurements could be used to extrapolate the temperature of the drugbased on heat transfer characteristics of the material used to constructthe rigid tube 11036 (or the other portions of the drug delivery deviceproximate to the drug).

The first and second temperature sensors 11604 and 11606 may be outputtheir temperature measurements to the power and control system 11400,which may analyze the temperature measurements to determine an amount ofelectricity that must be supplied to the heating element 11602 toachieve a target drug temperature. Additionally, the temperaturemeasurements of the first and second temperature sensors 11604 and 11606may be analyzed by the power and control system 11400 according tothermal dilution techniques in order to determine the flow rate of thedrug. Furthermore, in an embodiment where the drug delivery deviceincorporates a motor-controlled regulating mechanism to control theexpansion of the piston biasing member (e.g., akin to the drug deliverydevice 6010 or 8000), the power and control system 11400 may control themotor (e.g., the motor 6207 or any other motor described herein) basedon the output of the first and second temperature sensors 11604 and11606 to reduce the flow rate if the drug has not been sufficientlywarmed by the heating element 11602, so that the patient does notexperience a painful injection due to cold temperatures. Furthermore,input from the first and second temperature sensors 11604 and 11606 maybe used to determine if the drug has been overheated by the heatingelement 11602 and therefore no longer suitable for injection, in whichcase the drive mechanism 11100 may be locked out. Additional temperaturesensors may be included to monitor the temperature of the drug in thecontainer during, for example, storage to determine if the drug has beenstored at an appropriate temperature. If not, the power and controlsystem 11400 may lockout the device and/or alert the patient that thedrug is no longer viable.

The temperature control system 11600 may additionally includetemperature indicators (e.g., lights, sounds, graphical displays, etc.)or other output devices for informing the user of the drug temperatureand/or whether the drug temperature is suitable for injection.

While the embodiment of the tubular conduit illustrated in FIG. 188incorporates two flexible tubes and a rigid tube connected therebetween,alternative embodiments may forgo the rigid tube so that the tubularconduit is formed by a single, unitary flexible tube. In such anembodiment, the heating element 11602 may be wrapped around the single,unitary flexible tube.

In one alternative embodiment, the power and control system 11400 mayserve as the heating element 11602, or as a supplemental heatingelement. The power and control system 11400 may include a circuit boardand/or other electronics that heat up while performing their dataprocessing functions. By positioning the circuit board and/or otherelectronics immediately adjacent to the tubular conduit 11030 (e.g.,immediately above the tubular conduit 11030), the heat generated by thecircuit board and/or other electronics can be used to warm the drug asit flows through the tubular conduit 11030. Also, in some embodiments,it may be desirable that the heat generated by the power and controlsystem 11400 is not permitted to warm the drug. In such embodiments, thepower and control system 11400 may include a heat sink that is remotefrom the drug container, the fluid pathway connector, and/or theinsertion mechanism, so that the heat sink can draw heat away fromregions of the drug delivery device including the drug.

While the heating element 11602 described above generates heat primarilythrough electrical resistance, other embodiments of the heating elementmay generate heat through other means, including, but not limited to,induction, the Peltier effect, and/or a chemical reaction.

Furthermore, other embodiments of the temperature control system 11600may include a cooling system (not illustrated) for lowering thetemperature of the drug while it is disposed in the container 11050and/or flows through the tubular conduit 11030. Such a cooling systemmay employ a fan which draws in cool air from outside the drug deliverydevice and/or expels warm air from inside the drug delivery device.Alternatively, or additionally, the cooling system may employ thefollowing to reduce the temperature of the drug: a thermoelectriccooling element the exploits the Peltier effect and/or a chemicalreaction.

XXIII. Skin Attachment

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-188 may be configured to incorporate the embodiments of the skinattachment members described below in connection with FIG. 189A-194C,where appropriate.

The drug delivery devices of the present disclosure may be configuredfor temporary attachment to a patient's body tissue (e.g., the patient'sskin) while the drug is delivered. The drug delivery device may beattached to the tissue of the patient's abdomen, thigh, arm or someother portion of the patient's body. As described above, an adhesivepatch (e.g., the adhesive patch 26) may be disposed on or over a base ofthe housing to adhere the drug delivery device to the patient's bodytissue. The adhesive surface of the adhesive patch may initially becovered by a non-adhesive patch liner (e.g., the non-adhesive patchliner 28), which is removed from the adhesive patch 26 prior toplacement of the drug delivery device in contact with the patient's bodytissue.

Disengaging the adhesive from the patient's body tissue may cause topatient discomfort, particularly if the adhesive engages a large surfacearea of the patient's body tissue. Therefore, to reduce the amount ofbody tissue in contact with adhesive, only a limited portion of drugdelivery device's base may be covered with adhesive. FIGS. 189A and 189Billustrate, respectively, adhesive patches 12000 and 12100 which reducethe amount body tissue in contact with adhesive, yet still provideadequate adhesion to secure the drug delivery device to the patient'sbody tissue during drug delivery. The adhesive patches 12000 and 12100each may be applied to the base of any one of the drug delivery devicesdisclosed herein, including, but not limited to, any one of the drugdelivery devices 10, 910, 6010, 8000, 9010, 9210, 9310, 9410, 9510,9610, 11600, 12340, 12710, 11010, 13100, 19010, or 19020.

FIG. 189A shows that the adhesive patch 12000 includes a pattern ofadhesive dots 12002 with non-adhesive regions 12004 locatedtherebetween. The illustrated pattern is symmetric and includesequally-spaced rows and columns of circular adhesive dots 12202.Alternative embodiments may have a non-symmetric pattern and/ornon-circular adhesive dots. The adhesive patch 12000 includes a base12006 having a first side (not illustrated) for attachment to the drugdelivery device and an opposite second side 12006 including the patternof adhesive dots 12002. In alternative embodiments, the base 12006 maybe omitted, and the pattern of adhesive dots 12002 may be applieddirectly to an exterior surface of the drug delivery device.

Instead of adhesive dots, the adhesive patch 12100 shown in FIG. 189Bincludes a plurality of adhesive strips 12102, with non-adhesive regions12104 located therebetween. The adhesive strips 12102 are equally-spacedand extend lengthwise across the adhesive patch 12100. Alternativeembodiments may have non-linear (e.g., curved) adhesive strips and/orthe adhesive strips may extend widthwise across the adhesive patch12100. The adhesive patch 12100 includes a base 12106 having a firstside (not illustrated) for attachment to the drug delivery device and anopposite second side 12106 including the adhesive strips 12102. Inalternative embodiments, the base 12106 may be omitted, and the patternof adhesive strips 12102 may be applied directly to an exterior surfaceof the drug delivery device. A non-adhesive patch liner (e.g., thenon-adhesive patch liner 28) may be used to cover the adhesive sides ofeach of the adhesive patches 12100 and 12200 prior to use.

FIG. 190 illustrates an embodiment of a non-adhesive patch liner,denoted by reference numeral 12300, including stiffening members 12310for imparting rigidity to the non-adhesive patch liner 12300 as well asan adhesive patch (e.g., the adhesive patch 28, 12100, or 12200) coveredby the non-adhesive patch liner 12300. A body 12312 of the non-adhesivepatch liner 12300 may be co-extensive with the adhesive patch to preventunintended adhesion prior to use of the drug delivery device. Thestiffening members 12310 may each be made of a more rigid material(e.g., metal or hardened plastic) than the body 12312 of thenon-adhesive patch liner 12300. Additionally, as shown in FIG. 190, eachof the stiffening members 12310 may have a tapered shape, with a widththat narrows as the stiffening member 12310 approaches the outerperipheral edge of the body 12312. The rigidity imparted by thestiffening members 12300 to the outer peripheral edge of the adhesivepatch, which may extend beyond the outer edge of the body of the drugdelivery 12340 device as shown in FIG. 190, renders the outer peripheraledge of the adhesive patch less likely to experience curling.Accordingly, the stiffening members 12310 may help the adhesive patchretain its planar shape so that the patient can press the adhesive patchflushly against the patient's body tissue upon removal of thenon-adhesive patch liner 12300.

While the embodiment of the non-adhesive patch liner illustrated in FIG.190 includes stiffening members located at discrete points around theperiphery of the non-adhesive patch liner, other embodiments of thenon-adhesive patch liner may include a stiffening member that extendscontinuously around the periphery of the non-adhesive patch liner. FIG.191A illustrates an exploded assembly view of a non-adhesive patch liner12400, an adhesive patch 12500, and a base 12600 of a drug deliverydevice. The adhesive patch 12500 may be similar to one of the adhesivepatches disclosed herein, including, but not limited to, any one of theadhesive patches 28, 12100, or 12200. The non-adhesive patch liner 12400may include a central body portion 12402 and a ring-shaped stiffeningportion 12404 positioned around the periphery of the central bodyportion 12402 (as seen in the assembled view shown in FIG. 191B). Thecentral body portion 12402 may cover a central portion of the adhesivepatch 12500, leaving an outer peripheral edge of the adhesive patch12500 exposed. The ring-shaped stiffening portion 12404 may be used tocover this exposed outer peripheral edge of the adhesive patch 12500,thereby preventing it from curling. In some embodiments, the ring-shapedstiffening portion 12404 may cover and contact each of: an outerperipheral edge of the central body portion 12402, an outer peripheraledge of the adhesive patch 12500, and a portion of the base 12600 of thedrug delivery device surrounding the adhesive patch 12500. In such anembodiment, the underside of the ring-shaped stiffening portion 12404may be include an adhesive for adhering the ring-shaped stiffeningportion 12404 directly to the base 12600 of the drug delivery device andthe central body portion 12402. As such, removing the central bodyportion 12402 (e.g., by pulling a tab extending from the central body12402) may disengage the ring-shaped stiffening portion 12404 from thebase 12600 of the drug delivery device as well as the adhesive patch12500.

While the stiffening members described above may be attached to orintegrally formed with the non-adhesive patch liner, alternativeembodiments of the stiffening members may be attached to or integrallyformed with the adhesive patch. FIG. 192 illustrates a drug deliverydevice 12710 (which may correspond to any one of the drug deliverydevices disclosed herein, including, but not limited to, any one of thedrug delivery devices 10, 910, 6010, 8000, 9010, 9210, 9310, 9410, 9510,9610, 11600, 12340, 12710, 11010, 13100, 19010, or 19020) including ahousing 12712, an adhesive patch 12726 attached to the underside of thehousing 12712, and a non-adhesive patch liner 12728 removably attachedto the underside of the adhesive patch 12726.

The adhesive patch 12726 may include a base 12730 and a plurality ofstiffening members 12732. The base 12730 may have an upper surface 12734rigidly attached to the underside of the housing 12712 and a lowersurface (hidden in FIG. 192) covered with a skin adhesive. The base12730 may have a larger footprint than the housing 12712 such that anouter peripheral portion 12736 of the base 12730 forms a skirt thatextends beyond the outer edge of the housing 12712.

Still referring to FIG. 192, the stiffening members 12732 may be formedin the outer peripheral portion 12736 of the base 12730. In theillustrated embodiment, the stiffening members 12732 and the base 12730are integrally formed such that the stiffening members 12732 and thebase 12730 form a single, unitary structure made of a single material.Alternatively, the stiffening members 12732 may be distinct structuresfrom the base 12730. As illustrated in FIG. 192, the stiffening members12732 may be designed as a plurality of equally spaced ribs located atdiscrete locations around the periphery of the base 12730. Furthermore,the stiffening members 12732 may protrude upwardly from the uppersurface 12734 of the outer peripheral portion 12736 of the base 12730.Nevertheless, the height of the stiffening members 12732 may be suchthat the tops of the stiffening members 12732 are located below thebottom surface of the housing 12712.

The stiffening members 12732 may impart rigidity to the adhesive patch12726 so that the adhesive patch 12726 can retain its generally planarshape. Accordingly, the periphery of the adhesive patch 12726 is lesslikely to fold over on itself, or experience, curling when the drugdelivery device 12710 is being applied to the patient's skin or when thenon-adhesive patch liner 12728 is being removed.

Referring to FIG. 193, in at least one embodiment, the non-adhesivepatch liner 12728 may be comprised of separate first and second sections12740 and 12742 covering respective portions of the underside of theadhesive patch 12726. The first section 12740 may have a first tab 12744which protrudes outwardly from a side of the adhesive patch 12726, andthe second section 12742 may have a second tab 12746 which protrudesoutwardly from an opposite side of the adhesive patch 12726. The firstand second sections 12740 and 12742 may be removed separately bypulling, respectively, on the first and second tabs 12744 and 12746, asdescribed below with reference to FIGS. 192A-8192C.

In at least one embodiment, the process of attaching the drug deliverydevice 12710 to the patient's skin 12750 may involve the followingsteps. Initially, the non-adhesive patch liner 12728 may be disposedagainst the patient's skin 12750. Next, while the user or patient pushesdown on a first end 12752 of the housing 12712 (opposite to the firsttab 12744), the first tab 12744 may be pulled outwardly to remove thefirst section 12740 of the non-adhesive patch liner 12728 from theadhesive patch 12726, as illustrated in FIG. 192A. Subsequently, whilethe user or patient pushes down on a second end 12754 of the housing12712 (opposite to the second tab 12746), the second tab 12746 may bepulled outwardly to remove the second section 12742 of the non-adhesivepatch liner 12728 from the adhesive patch 12726, as seen in FIG. 192B.This will result in the adhesive patch 12726 being flush with thepatient's skin 12750, as shown in FIG. 192C.

In some embodiments, such as the one illustrated in FIGS. 192A-192C, thefirst tab 12744 may be formed by a portion of the first section 12740 ofthe non-adhesive patch liner 12728 that is folded back on itself. Moreparticularly, the first section 12740 may have a first end 12760 incontact with the adhesive patch 12726 and a second end 12762 folded overthe first end 12760 and configured to initially contact the patient'sskin 12750. The second end 12762 may include the first tab 12744. Bypulling the first tab 12744 outwardly, the first end 12760 of the firstsection 12740 may unroll such that it is peeled away from the adhesivepatch 12726. This configuration of the first section 12740 of thenon-adhesive patch liner 12728 may facilitate the removal of the firstsection 12740 from the adhesive patch 12726 despite the drug deliverydevice 12710 being push against the patient's skin 12750, as shown inFIG. 192A.

Similarly, the second tab 12746 may be formed a portion of the secondsection 12742 of the non-adhesive patch liner 12728 that is folded backon itself. More particularly, the second section 12742 may have a firstend 12770 in contact with the adhesive patch 12726 and a second end12772 folded over the first end 12770 and configured to initiallycontact the patient's skin 12750. The second end 12772 may include thesecond tab 12746. By pulling the second tab 12746 outwardly, the secondend 12770 of the second section 12746 may unroll such that it is peeledaway from the adhesive patch 12726. Like the first section 12740, thisconfiguration of the second section 12742 of the non-adhesive patchliner 12728 may facilitate the removal of the second section 12742 fromthe adhesive patch 12728 despite the drug delivery device 12710 beingpush against the patient's skin 12750, as shown in FIG. 192B.

Attachment of the drug delivery devices disclosed herein to thepatient's body tissue is not limited to adhesive means. Instead of anadhesive patch, or as a supplement to an adhesive patch, the drugdelivery device may incorporate a pneumatic system for temporarilyattaching the drug delivery device to the patient's body tissue. Such apneumatic system may include at least one pressure communication channelor aperture which extends through a base of the drug delivery device anddistributes a negative fluid pressure across the base that draws bodytissue against the base. Embodiments of such adhesive and/or pneumaticsystems for temporarily attaching a drug delivery device to body tissueare described in U.S. Provisional Patent Application No. 62/117,420entitled “DRUG DELIVERY DEVICE WITH VACUUM ASSISTED SECUREMENT AND/ORFEEDBACK”, which is hereby incorporated by reference in its entirety forall purposes. Any one of the drug delivery devices disclosed herein,including, but not limited to, any one of the drug delivery devices 10,910, 6010, 8000, 9010, 9210, 9310, 9410, 9510, 9610, 11600, 12340,12710, 11010, 13100, 19010, or 19020, may be configured to incorporateone or more of the embodiments of the adhesive and/or pneumatic systemsfor temporarily attaching a drug delivery device to body tissue asdescribed in U.S. Provisional Patent Application No. 62/117,420.

In yet still further embodiments, the drug delivery devices disclosedherein may be temporarily attached to a patient's soft body tissue byway of a mechanism (e.g., a strap) that clamps or squeezes the drugdelivery device between the patient's soft body tissue and bones orother more rigid anatomical structures behind the soft body tissue.

XIV. Connectivity Aspects

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-194C may be configured to incorporate and/or communicate with theembodiments of the data processing system described below in connectionwith FIG. 195, where appropriate.

The drug delivery devices of the present disclosure may be configured toinclude various data processing functionalities and/or operate withinvarious data processing networks. Embodiments of such data processingfunctionalities and networks related to drug delivery devices aredisclosed in International Patent Application Publication No.WO/2015/187793, International Patent Application Publication No.WO/2015/187797, International Patent Application Publication No.WO/2015/187799, International Patent Application Publication No.WO/2015/187802, and International Patent Application Publication No.WO/2015/187805, each of which is hereby incorporated by reference in itsentirety for all purposes. Any one of the drug delivery devicesdisclosed herein, including, but not limited to, any one of the drugdelivery devices 10, 910, 6010, 8000, 9010, 9210, 9310, 9410, 9510,9610, 11600, 12340, 12710, 11010, 13100, 19010, or 19020, may beconfigured to incorporate one or more of the data processingfunctionalities and/or operate within one or more of the data processingnetworks disclosed in International Patent Application Publication No.WO/2015/187793, International Patent Application Publication No.WO/2015/187797, International Patent Application Publication No.WO/2015/187799, International Patent Application Publication No.WO/2015/187802, and International Patent Application Publication No.WO/2015/187805.

The presently-disclosed drug delivery devices, or data processingsystems in communication with the presently-disclosed drug deliverydevices, may be configured to determine of one or more states of thedrug delivery device, which states may be determined through the use ofone or more sensors in combination with one or more controllers. Thesensors may rely on mechanical, electrical or chemical sensingmechanisms, and the controllers may be mechanical, electrical, and/orelectro-mechanical. By way of example and not by way of limitation, thestates may relate to the operation of the drug delivery device, and/orto the condition of the drug delivery device. The drug delivery device,or data processing system in communication with the drug deliverydevice, may use the state determination to control the operation of thedrug delivery device, and/or may communicate the state determination toother devices, such as third-party servers that may collect, process,and/or further disseminate the state determinations received from thedrug delivery device. In at least one embodiment, the drug deliverydevice may communicate the state determination to one or more localcomputing devices, such as a mobile computing device (e.g., smartphone,smartwatch, tablet, laptop, etc.).

In at least one embodiment, a drug delivery device according to thepresent disclosure may communicate data related to the device or thepatient to a social support network. For example, the drug deliverydevice may monitor a patient's use of the device with sensors or othermeans, and link the patient to a support group who can encourage thepatient to comply with a treatment regimen (e.g., a therapeuticregimen). In this way, the drug delivery device may leverage thecapabilities of social networking services (e.g., Facebook, Twitter,etc.) to identify a support group whose advice the patient is likely tofollow, thereby increasing the likelihood of the patient's compliancewith his or her treatment regimen.

FIG. 195 illustrates an embodiment of a data processing network 13000 incommunication with a drug delivery device 13100 corresponding to any oneof the other drug delivery device disclosed herein (including, but notlimited to, any one of the drug delivery devices 10, 910, 6010, 8000,9010, 9210, 9310, 9410, 9510, 9610, 11600, 12340, 12710, 11010, 13100,19010, or 19020). The drug delivery device 13100 is associated with apatient 13102 who may use the drug delivery device 13100 to inject adrug as part of a treatment regime. The drug delivery device 13100 maycommunicate with a server 13104 via one or more intermediate computingdevices and/or one or more networks. In turn, the server 13104 maycommunicate with the drug delivery device 13100, the patient 13102, andone or more computing devices (with their associated parties) via one ormore intermediate computing devices and/or one or more networks. As isalso illustrated in FIG. 195, the server 13104 may communicate directlyand/or wirelessly with the wearable drug delivery device 13100, using a4G antenna for example.

Still referring to FIG. 195, the drug delivery device 13100 isillustrated as communicating with a mobile computing device 13110 (e.g.,a smartphone) via a first communication link 13112, and with a computingdevice (e.g., a personal computer or dedicated hub) 13114 via a secondcommunication link 13116. Both links 13112 and 13116 may operateaccording to a near field communication protocol, such as Bluetooth, forexample. The mobile computing device 13110 may communicate with acellular network 13118 via a communication link 13120, while thecomputing device 13114 may communicate with a hard-wired network (e.g.,local area network or wide area network) 13122 via a communication link13124. These networks 13118 and 122 may also communicate with the server13104.

The networks 13118 and 13122 may facilitate communication between theserver 13104 and one or more parties associated with the patient 13102,such as his or her caregiver 13130, support giver 13132, and healthcareprovider 13134, via their mobile computing devices (e.g., smartphones).The server 13104 may also be in communication with one or more computingdevices (e.g., servers) associated with one or more additional partiesassociated with the patient 13102. For example, a healthcare systemserver 13140, a payment server 13142, a pharmacy server 13144, adistributor server 13146, and a governmental agency server 13148 areillustrated in communication with the server 13104 via the network13122. It will also be recognized that the networks 13118 and 13122 maybe in communication with each other.

In at least one embodiment, the mobile computing device 13110 mayinclude a processor (e.g., microprocessor) and a memory (e.g., a randomaccess memory (RAM), a non-volatile memory such as a hard disk, a flashmemory, a removable memory, a non-removable memory, etc.) for storingcomputer-executable instructions to be executed by the processor. Insome embodiments, the computer-executable instructions may be includedin a software application (e.g., a mobile software application, alsocommonly referred to as a “mobile app”) stored in the memory of themobile computing device 13110. The software application may be installedon the mobile computing device 13110 as one or more downloaded files,such as an executable package installation file downloaded from asuitable application store via a connection to the Internet. Examples ofpackage download files may include downloads via the iTunes store, theGoogle Play Store, the Windows Phone Store, downloading a packageinstallation file from another computing device, etc. The softwareapplication may be developed for a mobile operating system such asAndroid™ or iOS®, developed by Google and Apple, respectively. In someembodiments, the application may be initiated by a user selecting anicon shown on a home screen of a display (e.g., a touchscreen) of themobile computing device 13110. Various displays, including those havinginformational prompts and/or instructional prompts similar to thoseshown in the figures of International Patent Application Publication No.WO/2015/187797, may be generated in the software application anddisplayed to a user and/or patient via the display of the mobilecomputing device 13110.

XXV. Energy Management

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-195 may be configured to incorporate the embodiments of the energymanagement mechanisms described below in connection with FIG. 196A-200,where appropriate.

As described above, the drug delivery devices of the present disclosuremay incorporate a drive mechanism including one or more springs toprovide energy for moving a plunger seal to expel a drug from acontainer. The use of springs can offer benefits of simplicity and lowcost, but can have certain limitations.

There is a linear relationship between force and displacement in springactuators. To provide sufficient energy for drug delivery at the end ofthe stroke of the plunger seal, an excessive amount of energy may beinput to the system as drug delivery commences.

Further, as higher viscosity drugs are delivered via drug deliverydevices, requisite spring forces can increase. Springs with higherspring constants transmit more force to the drug product and container.Because kinetic energy is proportional to velocity squared, evenincremental increases in the spring constant can result in large changesin the net kinetic energy applied to the drug and container.

The patient may feel this excessive energy as a “slap” or similarphysical “bump”, as the spring-driven piston impacts the plunger seal ofthe container storing the drug. It is known that such mechanical bumpscan also be distracting or disturbing to users of the injectors and cantherefore prevent proper dose completion. It is therefore desirable toeliminate such disturbances.

Accordingly, a need exists for a drug delivery device with an energymanagement system which can maintain the intended spring force load ofthe drive mechanism while reducing the transmitted force and resultantenergy to the drug product, thereby reducing the potential forstructural damage to the container or other components of the drugdelivery device. Such a drug delivery device may be potentially morecomfortable and safer to use, and applicable to a greater range ofdrugs.

The drug delivery devices of the present disclosure may be configured toinclude an energy management system that maintains the intended springforce load of the drive mechanism while reducing the transmitted forceand resultant energy to the drug product. Embodiments of such energymanagement systems are disclosed in International Patent Application No.PCT/US15/29485 entitled “AUTOINJECTOR WITH SHOCK REDUCING ELEMENTS” andInternational Patent Application Publication No. WO/2016/003813,International Patent Application Publication No. WO/2015/187799, each ofwhich is hereby incorporated by reference in its entirety for allpurposes. Any one of the drug delivery devices disclosed herein,including, but not limited to, any one of the drug delivery devices 10,910, 6010, 8000, 9010, 9210, 9310, 9410, 9510, 9610, 11600, 12340,12710, 11010, 13100, 19010, or 19020, may be configured to incorporateone or more of aspects, features, and/or functionalities of the energymanagement systems disclosed in International Patent Application No.PCT/US15/29485 and International Patent Application Publication No.WO/2015/187799.

FIGS. 196A-196C, 197A-197C, and 198A-198C illustrate, respectively,assemblies 14000 a, 14000 b, 14000 c, each of which includes a drugcontainer 14050 (which may correspond to, but is not limited to, any oneof the container 50, 350, 618, 718, 818, 918, 1050, 6050, 8050, or9050), a drive mechanism 14100 (which may correspond to, but is notlimited to, any one of the drive mechanism 100, 130, 1100, 2100, 6100,8100, 8130 11100, 14100, 23090, or 90100), a fluid pathway connector14300 (which may correspond to, but is not limited to, any one of thefluid pathway connector 300, 622, 722, 822, 922, 1122, 1222, 1300, 2300,8300, 18300, 23030, 90300 182300, 230330, or 230130), and a drive dampermechanism 14170 a, 14170 b, or 14170 c that functions as an energymanagement system. The assemblies 14000 a, 14000 b, and 14000 c each maybe implemented in any one of the drug delivery devices disclosed herein,including, but not limited to, any one of the drug delivery devices 10,910, 6010, 8000, 9010, 9210, 9310, 9410, 9510, 9610, 11600, 12340,12710, 11010, 13100, 19010, or 19020.

The drug container 14050 may include a barrel 14058 and a plunger seal14060 moveable through the barrel 14058 to discharge a drug 14038 fromthe barrel 14058, and a pierceable seal (not illustrated) controllingaccess to an interior of the barrel 14058. The drive mechanism 14100 mayinclude a drive housing 14130, a piston 14110 moveable relative to thedrive housing 14130 and configured to impart movement to the plungerseal 14060, and a piston biasing member 14106 disposed between the drivehousing 14130 and the piston 14110. The piston 14110 may include a headmember 14148 disposed at its distal end.

The drive damper mechanism 14170 reduces the velocity of the piston14110 while retaining the intended force of the drive mechanism 14100,before the piston 14110 begins to move the plunger seal 14060 distallythrough the barrel 14058. By reducing the velocity of the piston 14110,the damper mechanism 14170 essentially operates as a shock reducingelement, as it reduces the kinetic energy applied to the drug 14038 andthe drug container 14050. The damper mechanism 14170 can be adapted toreduce the velocity of the piston 14110 to ensure that pressuredelivered to the system does not induce syringe breakage, pressuredelivered to the system prevents appreciable “slap” or discomfort to thepatient, and/or pressure delivered to the drug 14038 prevents shearforces from damaging the drug 14038.

In some embodiments, the drive damper mechanism can be adapted to reducethe velocity of the piston by less than 1%. In other embodiments, thedrive damper mechanism can be adapted to reduce the velocity of thepiston by about 1-5%. In further embodiments, the drive damper mechanismcan be adapted to reduce the velocity of the piston by about 5-10%. Infurther embodiments, the drive damper mechanism can be adapted to reducethe velocity of the piston by about 10-15%. In further embodiments, thedrive damper mechanism can be adapted to reduce the velocity of thepiston by about 15-20%. In further embodiments, the drive dampermechanism can be adapted to reduce the velocity of the piston by about20-30%. In still further embodiments, the drive damper mechanism can beadapted to reduce the velocity of the piston by about 30-50%. In yetfurther embodiments, the drive damper mechanism can be adapted to reducethe velocity of the piston by about 51%-100%. The reduction in velocityprovided by the drive damper mechanism can be selected to prevent aphysical disturbance and/or discomfort to the patient by preventingappreciable “slap”, and/or reduce breakage of the drug storage device,and/or reduce drug product damage caused by shear load, and/or allow theinjection device to be used for injecting drugs with higher viscosities.

As shown in FIGS. 196A-196C, the damper mechanism 14170 can be disposedinline between the plunger seal 14060 of the drug container 14050 andthe plunger head 14148 of the piston 14110 to minimize the size of theassembly 14000 a and to more effectively damp the motion of piston 14110at the plunger head/stopper interface. In other embodiments, as shown inFIGS. 197A-8197C, the drive damper mechanism can be disposed inlinebetween the proximal end of the piston 14110 of the drive mechanism andthe main housing of the drug delivery device. In further embodiments,the drive damper mechanism can be integrated into the piston.

In accordance with various embodiments of the assembly 14000 a, thedamper mechanism 14170 may comprise a dashpot. The dashpot uses viscousfriction to resist the motion of the piston 14110, thereby reducing thevelocity of the piston 14110. FIGS. 196A-196C depict an exemplaryembodiment of a linear dashpot 14172 that can be used in the assembly14000 a. As shown, the linear dashpot 14172 includes a drive dampingmechanism housing 14174, a working fluid 14178 contained inside thehousing 14174, and a piston assembly 14176 movably disposed within thehousing 14174. The housing 14174 can comprise a cylindrical sidewall14174 sw that is closed at each of its first and second ends by an endwall 14174 ew. In some embodiments, the housing 14174 can be made of arigid material, such as a plastic or a metal. The working fluid 14178contained within the housing 14174 can comprise, without limitation, oil(e.g., mineral oil), silicone material, water or air.

As shown in FIGS. 196A-8196C, the piston assembly 14176 may comprise apiston 14180 and a rod 14184 for pushing the piston 14180 through thehousing 14174. In other embodiments, such as shown in FIGS. 196A-196C,the piston rod can be configured and adapted to pull the piston throughthe dashpot housing 14174. As shown in FIGS. 196A-196C, the piston 14180can comprise a single disc-like structure or member 14182 (piston discmember 14182) having leading and trailing surfaces 141821 and 14182 t,respectively. The piston rod 14184 extends through an aperture 14174 ain one of the end walls 14174 ew of the housing 14174 and can have oneend attached to or unitary with the leading surface 141821 or trailingsurface 14182 t of the piston disc member 14182, depending upon whetherit pushes (see FIGS. 196A-196C) or pulls (FIGS. 197A-197C) the pistondisc member 14182 in the damping stroke. The free end of the piston rod14184, which is typically disposed external to the housing 14174, can beattached to the plunger head 14148, as shown in FIGS. 196A-196C. A seal,such as an O-ring (not visible), may be provided in or adjacent to theaperture 14174 a to prevent the working fluid 14178 from leaking out ofthe housing 14174 between the piston rod 14184 and the aperture 14174 ain the end wall 14174 ew of the housing 14174. In some embodiments, thepiston assembly 14176 can be made of a rigid material, such as a plasticor a metal. In other embodiments, the piston assembly 14176 can be madeof a resilient material, such as a natural or synthetic polymer. Instill further embodiments, the piston assembly 14176 can be made of aporous, rigid material.

FIGS. 196A-196C depict one exemplary mode of operation of the dashpot14172. As shown in FIG. 196A, upon the actuation of the drive triggeringmechanism, the energy source (e.g., piston biasing member 14106) of thedrive mechanism 14100 advances the piston 14110 toward plunger seal14060 disposed in the barrel 14058 of the drug container 14050. Once thelinear dashpot 14172 contacts the plunger seal 14060, as shown in FIG.196B, the load from the piston biasing member 14106 begins to betransmitted to the linear dashpot 14172, thereby causing the workingfluid 178 located in front of the dashpot piston disc member 14182 to bepushed or displaced through one or more constrictions to a locationbehind the piston disc member 14182 as the piston disc member 14182moves from one end of the housing 14174 to the other. The flow of theworking fluid 14178 through the one or more constrictions generates aviscous friction, which resists the movement of the piston disc member14182, thereby damping plunger motion. In some embodiments in which thepiston disc member 14182 is made of a rigid material, theconstriction(s) can comprise a small gap (not shown) between theperipheral edge of the piston disc member 14182 and the sidewall 174 swof the dashpot housing 14174. In other embodiments, the constriction(s)further or alternatively comprise one or more grooves 14186 provided inthe peripheral edge of the piston disc member and/or one or moreopenings extending through the piston disc member 14182 through whichthe working fluid 178 flows as it is displaced from in front of thepiston disc member 14182, to behind the piston disc member 14182. Inother embodiments in which the piston disc member 14182 is made of aresilient material, the peripheral edge of the piston disc member 14182can bend backwards enough to generate a narrow gap or constrictionbetween the peripheral edge of the piston disc member 14182 and thesidewall 174 sw of the dashpot housing 14174 (not shown) so that theworking fluid 178 can flow therethrough. In other embodiments in whichthe piston disc member 14182 is made of a porous material, the workingfluid 178 will flow through the pores (constrictions) of the piston discmember 14182. In each of these embodiments, the one or moreconstrictions of the linear dashpot 14172 provide a velocity-dependentresistance to the force of the energy source 144 (e.g., piston biasingmember 14106) acting on the piston 14110. This resistance, when coupledto the piston 14110, reduces the velocity of the piston 14110 whilemaintaining the force of the energy source 144 (e.g., piston biasingmember 14106) before the piston 14110 starts to move the plunger seal14060. The size, number and type of constrictions, the type of workingfluid 178 used in the linear dashpot 14172, the configuration of thehousing 14174 and piston assembly 14176, and any combination thereof,can be adjusted and/or selected to allow the damping characteristics ofthe damper mechanism 14170 to be tuned to properly damp the shockcharacteristics of the drive mechanism 14100.

As shown in FIG. 196C, the piston disc member 14182 engages the leadingone of the end walls of the dashpot housing 14174, and the force of thepiston biasing member 14106 moves the plunger seal 14060, linear dashpot14172 and piston 14110 distally through the barrel 14058 of the drugcontainer 14050 at a reduced velocity, to expel the drug 14038 from thebarrel 14058.

FIGS. 197A-197C depict one exemplary mode of operation of a dashpot14192 disposed inline between the proximal end 14146 pe of the pistonrod 14146 of the injection drive mechanism and the main housing of thedrug delivery device. In this embodiment, the dashpot housing 14194 canbe retained in a tubular support member 14122 of the main housing by adetent 14123 integrally formed with the tubular support member 14122.Such an arrangement can be provided on a cantilever spring 14125 definedin the tubular support member 14122. The end of the piston rod 14204disposed within the dashpot housing 14194 can be attached to the leadingsurface 142021 of the piston disc member 14202 and the free end of thepiston rod 14204 can be attached to the proximal end 14146 pe of thepiston rod 14146 such that as the piston rod 14146 is driven distally bythe energy source (e.g., piston biasing member 14106). The piston rod14204 pulls the piston disc member 14202 through the dashpot housing14194.

As shown in FIGS. 197A-197C, upon the actuation of the drive triggeringmechanism, the energy source (e.g., piston biasing member 14106) of theinjection drive mechanism begins to advance the piston 14110 toward theplunger seal 14060 disposed in the barrel 14058 of the drug container14050. The load applied by the piston biasing member 14106 to the piston14110 can be transmitted to the dashpot 14192. The working fluid 194located in front of the piston disc member 14202 is pushed or displacedthrough the one or more constrictions to a location behind the pistondisc member 14202, as the piston disc member 14202 is pulled from oneend of the dashpot housing 14194 to the other. The resistance generatedby the working fluid 14198 flowing through the one or more constrictionsmaintains the force of the piston biasing member 14106 while reducingthe velocity of the piston 14110 before the head member of the piston14110 impacts the plunger seal 14060. The head member of the piston14110 impacts the plunger seal 14060 at the reduced velocity, and theforce of the energy source (e.g., piston biasing member 14106) begins tomove the plunger seal 14060 and piston 14110 distally through the barrel14058 of the drug container 14050, to expel the drug 14038 from thebarrel 14058. At about the same time, the piston disc member 14202 ofthe dashpot 14192 reaches the end of its stroke and engages the leadingend wall 194 ew of the dashpot housing 14194. The energy source (e.g.,piston biasing member 14106) can be selected to apply enough energy tothe piston 14110 to overcome the detent and cantilever arrangement123/125 so that it releases the dashpot 14192 from the tubular supportmember 14122 to allow for movement of the piston 14110 as the energysource (e.g., piston biasing member 14106) drives the piston 14110,plunger seal 14060, and drug 14038 through the barrel 14058 of the drugcontainer 14050. The release of the dashpot 14192 from the tubularsupport member 14122 reduces the duration of engagement, which allowsthe overall length of the injection device to be reduced.

FIGS. 198A-198C depict an exemplary mode of operation of dashpot 14212that is integrated into piston 14242. As shown in FIGS. 198A-198C, theintegrated dashpot 14212 includes a housing 14214 formed by a tubularwall 14214 t and plunger head 14248, which closes the open distal end ofthe tubular wall 14214 t. The dashpot 14212 further includes a pistonformed by a distal end wall 14220 of hollow plunger rod 14246, which isinitially disposed in the open proximal end of the tubular wall 14214 tof the dashpot housing 14214. The working fluid 14218 of the dashpot14212 is initially provided in the dashpot housing 14214, in front ofthe distal end wall 14220 of the plunger rod 14246. As shown in FIG.198A, upon actuation of the drive triggering mechanism (not shown), theenergy source (e.g., spring 14244 s) of the injection drive mechanismapplies a force to the plunger rod 14246 and advances the piston 14242toward plunger seal 14060 disposed in the barrel 14058 of the drugcontainer 14050. Once the plunger head 14248 makes contact with theplunger seal 14060, as shown in FIG. 198B, the load from the spring14244 s is transmitted to the dashpot 14212 integrally formed in thepiston 14242. The working fluid 14218 located in front of the end wall220 of the plunger rod 14246 is pushed or displaced through one or moreconstrictions (as previously described) provided in the end wall 220 andinto the space defined by the hollow plunger rod 14246, behind the endwall 220 as it moves distally into the dashpot housing 14214. Theresistance or damping provided by dashpot 14212 reduces the velocity ofthe plunger rod 14246 before the plunger rod 14246 engages the plungerhead 14248 to move the plunger seal 14060, and performs the dampingwhile maintaining the force of the spring 14244 s.

As shown in FIG. 198C, the end wall 220 of the plunger rod 14246 engagesthe plunger head 14248, which marks the end of the damping stroke of thedashpot. The spring 14244 s then propels or forces the plunger rod 14246and plunger head 14248 as a single component (i.e., the plunger) againstthe plunger seal 14060 to drive the plunger seal 14060 distally throughthe barrel 14058 of the drug container 14050, to expel the drug 14038from the barrel 14058.

FIG. 199 shows another exemplary embodiment of the dashpot. The dashpot14270 is substantially similar to the dashpots previously describedexcept that the piston of the piston assembly 14276 comprises two ormore disc members 14282 spaced apart from one another along the pistonrod 14284. The two or more piston disc members 14282 and the previouslydescribed constrictions, which may be associated with each piston discmember 14282, provide a series of resistances to piston movement, whereeach of the resistances can be the same and/or different. The seriesresistance of the dashpot 14270 allows the velocity of the plunger to bereduced in stages or increments while maintaining the force of theenergy source (e.g. spring 14144 s). In some embodiments, the multi-discpiston assembly 14276 can be made of a rigid material, such as a plasticor a metal. In such embodiments, the constriction(s), which control ordefine the resistance provided by each piston disc member 14282, cancomprise a small gap (not shown) between the peripheral edge of one ormore of the piston disc members 14282 and the sidewall 14274 sw of thedashpot housing 14274. In other such embodiments, the constriction(s)can comprise one or more grooves provided in the peripheral edge of oneor more of the piston disc members 14182 or one or more openings 14188extending through the one or more piston disc members 14182, forming oneor more of the piston disc members as porous discs, and any combinationthereof. In other embodiments, the multi-disc piston assembly 14276 canbe made of a resilient material, such as a natural or syntheticelastomer, such that the marginal peripheral edge of each piston discmember 14282 can bend backwards enough to generate a narrow gap orconstriction between the peripheral edge of the piston disc members14282 and the sidewall 14274 sw of the dashpot housing 14274 so that theworking fluid can flow therethrough. If air is used as the workingfluid, the resilient piston disc members 282 of the piston assembly 276may be used to create a squeeze-film damping effect. Any of the dashpotsdescribed above with respect to FIGS. 196A-85C, 86A-86C, and 87A-87C,can utilize the piston assembly 14276 of FIG. 199.

FIG. 200 shows an exemplary embodiment of the dashpot of the presentdisclosure. The dashpot 14370 comprises a housing 14374 and a pistonassembly 14376 comprising a hollow piston rod 14384 and a pistonconfigured as a bellows-like structure (bellows piston structure)attached to an end of the piston rod 14384 disposed within the housing14374. The hollow piston rod 14384 may have an aperture 14384 a forexhausting working fluid (not shown) flowing through the hollow pistonrod 14384 outside of the dashpot housing 14374. The bellows pistonstructure can comprise one or more collapsible lobes that contain theworking fluid, which fluid can be air or any other suitable workingfluid. An opening 14386 (constriction) can be provided in the portionsof the lobe walls connecting each adjacent pair lobes of the bellowspiston structure to one another and to the hollow piston rod 14384. Theopenings 14386 allow the working fluid contained in the lobes to flowfrom one lobe to another, thereby functioning as constrictions. Thedashpot 14370 provides damping when the bellows piston structure ispushed or pulled into the end wall 14374 ew of the dashpot housing 14374and collapsed by the force acting on the plunger 14142 supplied by theenergy source (e.g., spring 14144 s) of the drive plunger mechanism. Thedamping action is provided as the working fluid contained inside thelobes flows through the openings 14386, the hollow piston rod 14384 andthe rod aperture 14384 a as the lobes of the bellows piston structureare collapsed. Any of the dashpots embodiments described above withrespect to FIGS. 196A-196C, 197A-197C, and 198A-198C, can utilize thepiston assembly 14376 of FIG. 200.

XXVI. Additional Embodiments Relating to Skin Attachment

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1A-200, may be configured to incorporate the embodiments of the adhesivedescribed below in connection with FIGS. 201A-202D.

The present embodiments disclose adhesives which have bond strengthswhich are sensitive to the presence of a stimulant. The adhesive may beused to adhere the drug delivery device to the skin of a patient. Theintroduction of a stimulus may cause the bond strength of the adhesiveto decrease such that the device may be more easily removed from thepatient's skin as well as possibly reducing the pain or discomfort tothe patient due to the removal. The stimulus may be chosen from any ofthe group of stimuli that is capable of decreasing the strength of thebond including: light, such as a UV light, heat, and electricity. Thestimulant source may be integrated into the medical device or,alternatively, may be independent from the medical device. Methods ofuse and assembly are also described.

As seen in FIGS. 201A-201C, the drug delivery device 19010 may include abody 19001, stimulant source 19002, first adhesive patch 19003, andsecond adhesive patch 19004. Body 19001 may encompass or enclosestimulant source 19002 or, alternatively, stimulant source 19002 may belocated on the outside of body 19001. The stimulant source 19002 has aninactive state and an active state. In the inactive state the stimulantsource does not produce and/or emit a stimulus. In the active state, thestimulant source does produce and emit a stimulus. The bond strength offirst adhesive 19003 may be such that it does not decrease in responseto activation of stimulant source 19002. The first adhesive may retainthe second adhesive in connection with the medical device. The bondstrength of second adhesive 19004 may initially have a first bondstrength in the absence of a stimulant and a second bond strength in thepresence of a stimulant. The device 190010 may, optionally, include aremovable adhesive cover which protects and isolates the adhesive duringshipment and prior to application of the medical device to the patient.

Prior to initiation of delivery of the medicament, the patient or amedical practitioner may remove the adhesive cover, if equipped. Themedical device may then be secured to the patient using the adhesive.The first bond strength of the second adhesive may be such that itsecurely attaches the device to the patient's skin, preventingunintentional removal. After delivery of the medicament or, at any otherdesired time, stimulant source 19002 may be activated. The activationmay occur automatically at completion of medicament delivery or mayoccur in response to an input by the patient. For example, the devicemay include a stimulant activation mechanism such as a button, switch,or any other mechanism known to one skilled in the art. Activation ofthe stimulant source causes the bond strength of at least a portion ofsecond adhesive patch 19004 to decrease to the second bond strength. Inat least one embodiment, the bond strength of the outer perimeter of thesecond adhesive may be decreased to the second bond strength, therebyallowing the user to easily engage the edge of the adhesive and therebyremove or peel off the remainder of the adhesive from the patient'sskin. In these embodiments, a stimulant source may be arranged aroundthe outer profile of the device, the position of the stimulant sourceand the intensity of the stimulant controlling the portion of the secondadhesive which is affected. In other embodiments, the bond strength ofsubstantially all of the second adhesive is decreased, thereby allowingeasy removal of the device from the patient's skin. The bond strength ofthe second adhesive does not need to be decreased uniformly in responseto activation of the stimulant source. In other words, the bond strengthof some portion of the second adhesive may be decreased to a greaterextent than other portions. The cohesive properties of the adhesive maybe completely eliminated or, alternatively, may retain some bondingstrength. For example, the bond strength of the adhesive, in thepresence of the activated stimulant may be sufficient to maintain itsadhesion to the patient's skin until a removal operation is performed bythe patient.

The stimulant may be a UV light source and be an integral aspect of thedevice as seen in FIGS. 201A-201C. The UV light source may be located onthe bottom portion of the device such that it is in proximity to theadhesive patch. The UV light source may be in electronic communicationwith one or more other aspects of the device such that activation of theUV light source may be performed and/or controlled by a PCB or othertype of electronic controller. Activation, by the electronic controller,may occur in response to completion of the delivery of a medicament tothe patient. The activation may also be triggered by an input by theuser, such as by depression of a button.

In other embodiments, shown in FIGS. 202A-202D, the stimulant source190015 is an external stimulant source (i.e., not physically connectedto the medical device). In these embodiments, the stimulant source maybe supplied, with the drug delivery device 19020, to the user or may besupplied separately. The external stimulant source may be used multipletimes and for multiple devices. To facilitate application of thestimulant to the adhesive, one or more aspects of the body of the devicemay be at least partially translucent, thereby allowing a stimulant suchas a UV light to pass through. In at least one embodiment, the medicaldevice may have a removable portion 19011. The removal of this portionof the medical device may expose a translucent portion 19012.Translucent portion 19012 may be a thin portion of the device therebyallowing the stimulant source to come into close proximity with theadhesive. A first adhesive 19013 may be bonded to translucent portion19012. The bond strength of the first adhesive may not be affected bythe presence of the stimulant. A second adhesive 19014 may be applied,the bond strength of which is altered by the presence of a stimulant asdescribed previously. The external stimulus may be in the form of ahandheld UV light source such that the user may direct the light sourcetoward the adhesive.

In another aspect of the invention, the secondary adhesive may bere-useable. Removal of the stimulant may allow the adhesive to return toits first bond strength. After returning to the first bond strength thedevice may be re-applied to the patient's skin. This may be useful inapplications of re-usable medical devices.

In applications in which the bond strength of the adhesive is affectedby light, the adhesive may be configured such that it responds only tolight of certain wavelengths. This may allow filters to be applied thatprevent an inadvertent decrease in bond strength.

The bond strength of the adhesive may be immediately decreased in thepresence of the stimulant. Alternatively, it may be necessary that theadhesive be exposed to the stimulus for a prolonged period of time inorder to decrease the bond strength. The time may be as short as a fewseconds to as long as a few minutes.

In other embodiments, a method of use is provided. The method of use mayinclude the steps of: applying a medical device to a patient's skinusing an adhesive; initiating operation of the medical device;activating a stimulant source to decrease the bond strength of at leasta portion of the adhesive; and removal of the medical device from thepatient. The stimulant source may be integral to the medical device ormay be independent from the device. The method may optionally alsoinclude the step of removing an adhesive patch cover. The method mayalso include removal of one or more portions of the medical device fromone or more other portions of the medical device.

In still other embodiments, a method of assembly is provided. The methodof assembly may include the steps of: applying a first adhesive to aportion of the medical device; applying a second adhesive at leastpartially to the second adhesive. The method of assembly may furtherinclude assembling a stimulant source into the medical device.

XXVII. Additional Embodiments of Fluid Pathway Connector

At least some of the drug delivery devices described in thisapplication, including at least those described in connection with FIGS.1-202D, may be configured to incorporate the embodiments of the fluidpathway connector described below in connection with FIGS. 203A-203C.The embodiments of the fluid pathway connector described below inconnection with FIGS. 203A-203C may be used to replace, in its entiretyor partially, the above-described fluid pathway connector 300, 622, 722,822, 1222, 1300, 2300, 6300, 8300, 14300, 18300, 90300, 94300, 95300,or, 96300, or any other fluid pathway connector described herein, whereappropriate.

In the processes of filling drug containers and other drug deliverydevices, it is sometimes necessary to connect two or more sterilecomponents or subassemblies. For example, wearable injectors or drugpumps may include a drug container which may be filled with a fluid drugusing standard pharmaceutical fill-finish processes. After filling ofthe drug container, it may be necessary to connect the drug container toone or more additional components or subassemblies such that a fluidcommunication may be established between the drug container and thesecomponents. Maintaining the fluid path in an aseptic condition iscritical, preventing the introduction of harmful microbes to the drugand/or fluid pathway. The connection of two or more aseptic componentsor subassemblies is typically performed in an aseptic environment, suchas a clean room, thereby ensuring that no harmful microbes areintroduced to the assembly. This, however, may lead to increased cost tomanufacture the drug delivery devices.

While many of the above-described embodiments of the fluid pathwayconnector incorporate a piercing member which moves to access the drugcontainer upon activation of the drug delivery device, alternativeembodiments of the fluid pathway connector, such as the embodimentillustrated in FIGS. 203A-203C, may include a piercing member thatremains stationary throughout drug delivery. In such alternativeembodiments, the drug container may move toward the stationary piercingmember upon activation of the drug delivery device. The movement of thedrug container may result in the stationary piercing member accessingthe drug container through the pierceable seal located at the distal endof the drug container.

FIGS. 203A-203C illustrate a subassembly of a drug delivery device(e.g., the drug delivery device 10, 910, 6010, 8000, 9010, 9210, 9310,9410, 9510, 9610, 11600, 12340, 12710, 11010, 13100, 19010, or 19020 orany other drug delivery device described herein) including a drugcontainer 10050 (which may be substituted for any one of the drugcontainers 300, 622, 722, 822, 922, 1122, 1222, 1300, 2300, 8300, 18300,23030, 90300 182300, 230330, or 230130, or any other fluid pathwayconnector described herein), a drive mechanism 10100 (which may besubstituted for any one of the drive mechanisms 100, 130, 1100, 2100,6100, 8100, 8130 11100, 14100, 23090, or 90100, or any other fluidpathway connector described herein) and a fluid pathway connector 10300.The drug container 10050 may include a barrel 10058, a plunger seal10060 moveable through the barrel 10058, and a pierceable seal 10056covering an open distal end of the barrel 10058 and controlling accessto the interior of the barrel 10058.

The drive mechanism 10100 may include a drive housing 10130, a piston10110 moveable relative to the drive housing 10130 and configured toimpart movement to the plunger seal 10060, and a piston biasing member10106 disposed between the drive housing 10130 and the piston 10110.Prior to delivery, the piston biasing member 10106 may be retained in apiston biasing member energized state, as depicted in FIG. 203A. Whenthe piston biasing member 10106 is released and consequentlyde-energizes (as seen in FIGS. 203B and 203C), the piston biasing member10106 may move the piston 10110 and/or the plunger seal 10060 toward thefluid pathway connector 10300.

The fluid pathway connector 10300 may define a sterile fluid flowpathbetween the drug container 10050 and an insertion mechanism (e.g., theneedle insertion mechanism 200, 624, 724, 824, 924, 1124, 1224, 6200,7200, 8200, 11200, 23070, 90200, 92200, 93200, 94200, 95200, or 96200,or any other insertion mechanism described herein). The fluid pathwayconnector 10300 may include a connection hub 10310, a tubular conduit(not illustrated) providing fluid communication between the connectionhub 10310 and the insertion mechanism, a piercing member 10330 (e.g., acontainer access needle) configured to pierce the pierceable seal 10056to establish fluid communication between the between the barrel 10058and the tubular conduit during drug delivery, a barrel connector 10332,and a flexible sealing member 10334. In some embodiments, the tubularconduit may be a single, unitary tube made of a flexible material andmay extend directly between the connection hub 10310 and the insertionmechanism. In other embodiments, depending on the need to regulate ormodify the fluid pressure, fluid flow rate, or other characteristic ofthe drug, the tubular conduit may include one or more flow restrictorsmade of a relatively rigid material and connected at opposite ends viaflexible tubes to the connection hub 10310 and the insertion mechanism,respectively.

Still referring to FIGS. 203A-203C, the flexible sealing member 10334may define a sterile chamber 10062 with a collapsible volume between thedistal end of the barrel 10058 and the connection hub 10310. In at leastone embodiment, the flexible sealing member 10334 may have a generallyconical shape and function as a flexible bellows. A proximal end of theflexible sealing member 10334 may be clamped between the barrelconnector 10332 and a distal end surface of the barrel 10058. At itsdistal end, the flexible sealing member 10334 may be connected to theconnection hub 10310.

The barrel connector 10332 may have a tubular body portion 10335configured to fit snugly around a circumferential surface of the barrel10058, and first and second radially inwardly depending annularprotrusions 10336, 10338 at opposite ends of the tubular body portion10335. The first annular protrusion 10336 may grip a neck of the barrel10058, and the second annular protrusion 10338 may clamp the proximalend of the flexible sealing member 10334 against the distal end surfaceof the barrel 10332.

The connection hub 10310 may be fixed relative to a housing (e.g., thehousing 12) of the drug delivery device such that the connection hub10310 is prevented from moving relative to the housing of the drugdelivery device. A distal end of the piercing member 10330 may berigidly connected to the connection hub 10310 so that the piercingmember 10330 is also fixed relative to the housing of the drug deliverydevice. The barrel 10058 may be slidably connected to the housing of thedrug delivery device such that the barrel 10058 can move (e.g.,translate in a linear direction) relative to the housing of the drugdelivery device. As the barrel 10058 moves toward the connection hub10310, the flexible sealing member 10334 may elastically orin-elastically deform such that the volume of the sterile chamber 10062decreases, as illustrated in FIGS. 203B and 203C.

In a pre-delivery state (FIG. 203A), a proximal end of the piercingmember 10330 may be disposed within the sterile chamber 10062 defined bythe flexible sealing member 10334. Upon release of the piston biasingmember 10106, the piston biasing member 10106 may begin to de-energizeand thereby cause the piston 10110 and the plunger seal 10060 to movetoward the piercing member 10330. Friction between the plunger seal10060 and the inner wall of the barrel 10058 may cause the barrel 10058,which is slidably connected to the housing, to initially move in adistal direction together with the plunger seal 10060. The movement ofthe barrel 10058 causes the pierceable seal 10056 to be pierced by thepiercing member 10330. As a result, the piercing member 10330 may accessthe interior of the barrel 10058 and establish fluid communicationbetween the barrel 10058 and the connection hub 10310.

FIG. 203B shows that the barrel 10058 continues to move in the distaldirection until it contacts a stopping member, which in the presentembodiment corresponds to the connection hub 10310. The reaction forceexerted on the barrel 10058 by the stopping member overcomes thefrictional force between the plunger seal 10060 and the inner wall ofthe barrel 10058, thereby allowing the plunger seal 10060 to moverelative to the barrel 10058 and discharge the drug from the barrel10058 via the piercing member 10330. FIG. 203C shows that movement ofthe plunger seal 10060 is halted, thereby ending drug delivery, when theplunger seal 10060 impacts a portion of the inner wall of the barrel10058 at the neck of the barrel 10058.

The combination of the fluid pathway connector 10300 having a stationarypiercing member 10330 and the drug container 10050 having a moveablebarrel 10058 removes the need for a separate mechanism to establishfluid communication with the interior of the barrel 10058 uponactivation of the drug delivery device. Instead, the force of the pistonbiasing member 10106 is utilized to move the pierceable seal 10056 intothe stationary piercing member 10330 to establish fluid communicationwith the interior of the barrel 10058. Accordingly, the design andmanufacture of the drug delivery device may be simplified, and theoverall size of the drug delivery device may be reduced.

XXVIII. Drug Information

The above description describes various systems and methods for use withvarious drug delivery devices. It should be clear that the systems, drugdelivery devices or methods can further comprise use of a medicamentlisted below with the caveat that the following list should neither beconsidered to be all inclusive nor limiting. The medicament will becontained in any one of the reservoirs or containers described herein,including, but not limited to, any one of the containers 50, 350, 618,718, 818, 918, 1050, 1118, 1850, 2050, 2330, 6050, 8050, 9050, 9250,9350, 9450, 9550, 9650, 11050, 14050, 23050, 230350, or 951050. In someinstances, the reservoir is a primary container that is either filled orpre-filled for treatment with the medicament. The primary container canbe a cartridge or a pre-filled syringe. Additionally, in some instances,the reservoir may be a primary container that is pre-loaded.

For example, the drug delivery device or more specifically the reservoirof the device may be filled with colony stimulating factors, such asgranulocyte colony-stimulating factor (G-CSF). Such G-CSF agentsinclude, but are not limited to, Neupogen® (filgrastim) and Neulasta®(pegfilgrastim). In various other embodiments, the drug delivery devicemay be used with various pharmaceutical products, such as anerythropoiesis stimulating agent (ESA), which may be in a liquid or alyophilized form. An ESA is any molecule that stimulates erythropoiesis,such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo®(epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta),Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon®(epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa),epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta),Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa,epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well asthe molecules or variants or analogs thereof as disclosed in thefollowing patents or patent applications, each of which is hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689;and PCT Publication Nos. WO 91/05867; WO 95/05465; WO 96/40772; WO00/24893; WO 01/81405; and WO 2007/136752.

An ESA can be an erythropoiesis stimulating protein. As used herein,“erythropoiesis stimulating protein” means any protein that directly orindirectly causes activation of the erythropoietin receptor, forexample, by binding to and causing dimerization of the receptor.Erythropoiesis stimulating proteins include erythropoietin and variants,analogs, or derivatives thereof that bind to and activate erythropoietinreceptor; antibodies that bind to erythropoietin receptor and activatethe receptor; or peptides that bind to and activate erythropoietinreceptor. Erythropoiesis stimulating proteins include, but are notlimited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega,epoetin iota, epoetin zeta, and analogs thereof, pegylatederythropoietin, carbamylated erythropoietin, mimetic peptides (includingEMP1/hematide), and mimetic antibodies. Exemplary erythropoiesisstimulating proteins include erythropoietin, darbepoetin, erythropoietinagonist variants, and peptides or antibodies that bind and activateerythropoietin receptor (and include compounds reported in U.S.Publication Nos. 2003/0215444 and 2006/0040858, the disclosures of eachof which is incorporated herein by reference in its entirety) as well aserythropoietin molecules or variants or analogs thereof as disclosed inthe following patents or patent applications, which are each hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086;6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369;7,030,226; 7,084,245; and 7,217,689; U.S. Publication Nos. 2002/0155998;2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694;2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834;2005/0096461; 2005/0107297; 2005/0107591; 2005/0124045; 2005/0124564;2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879; 2005/0158822;2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211;2005/0202538; 2005/0227289; 2005/0244409; 2006/0088906; and2006/0111279; and PCT Publication Nos. WO 91/05867; WO 95/05465; WO99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO2004/002417; WO 2004/002424; WO 2004/009627; WO 2004/024761; WO2004/033651; WO 2004/035603; WO 2004/043382; WO 2004/101600; WO2004/101606; WO 2004/101611; WO 2004/106373; WO 2004/018667; WO2005/001025; WO 2005/001136; WO 2005/021579; WO 2005/025606; WO2005/032460; WO 2005/051327; WO 2005/063808; WO 2005/063809; WO2005/070451; WO 2005/081687; WO 2005/084711; WO 2005/103076; WO2005/100403; WO 2005/092369; WO 2006/50959; WO 2006/02646; and WO2006/29094.

Examples of other pharmaceutical products for use with the device mayinclude, but are not limited to, antibodies such as Vectibix®(panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); otherbiological agents such as Enbrel® (etanercept, TNF-receptor/Fc fusionprotein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF,hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such asSensipar® (cinacalcet). The device may also be used with a therapeuticantibody, a polypeptide, a protein or other chemical, such as an iron,for example, ferumoxytol, iron dextrans, ferric glyconate, and ironsucrose. The pharmaceutical product may be in liquid form, orreconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins setforth below, including fusions, fragments, analogs, variants orderivatives thereof:

OPGL specific antibodies, peptibodies, and related proteins, and thelike (also referred to as RANKL specific antibodies, peptibodies and thelike), including fully humanized and human OPGL specific antibodies,particularly fully humanized monoclonal antibodies, including but notlimited to the antibodies described in PCT Publication No. WO 03/002713,which is incorporated herein in its entirety as to OPGL specificantibodies and antibody related proteins, particularly those having thesequences set forth therein, particularly, but not limited to, thosedenoted therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including theOPGL specific antibodies having either the light chain of SEQ ID NO:2 asset forth therein in FIG. 2 and/or the heavy chain of SEQ ID NO:4, asset forth therein in FIG. 4, each of which is individually andspecifically incorporated by reference herein in its entirety fully asdisclosed in the foregoing publication;

Myostatin binding proteins, peptibodies, and related proteins, and thelike, including myostatin specific peptibodies, particularly thosedescribed in U.S. Publication No. 2004/0181033 and PCT Publication No.WO 2004/058988, which are incorporated by reference herein in theirentirety particularly in parts pertinent to myostatin specificpeptibodies, including but not limited to peptibodies of the mTN8-19family, including those of SEQ ID NOS:305-351, including TN8-19-1through TN8-19-40, TN8-19 con1 and TN8-19 con2; peptibodies of the mL2family of SEQ ID NOS:357-383; the mL15 family of SEQ ID NOS:384-409; themL17 family of SEQ ID NOS:410-438; the mL20 family of SEQ IDNOS:439-446; the mL21 family of SEQ ID NOS:447-452; the mL24 family ofSEQ ID NOS:453-454; and those of SEQ ID NOS:615-631, each of which isindividually and specifically incorporated by reference herein in theirentirety fully as disclosed in the foregoing publication;

IL-4 receptor specific antibodies, peptibodies, and related proteins,and the like, particularly those that inhibit activities mediated bybinding of IL-4 and/or IL-13 to the receptor, including those describedin PCT Publication No. WO 2005/047331 or PCT Application No.PCT/US2004/37242 and in U.S. Publication No. 2005/112694, which areincorporated herein by reference in their entirety particularly in partspertinent to IL-4 receptor specific antibodies, particularly suchantibodies as are described therein, particularly, and withoutlimitation, those designated therein: L1H1; L1H2; L1H3; L1H4; L1H5;L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5;L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1;L5H1; L6H1, each of which is individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication;

Interleukin 1-receptor 1 (“IL1-R1”) specific antibodies, peptibodies,and related proteins, and the like, including but not limited to thosedescribed in U.S. Publication No. 2004/097712, which is incorporatedherein by reference in its entirety in parts pertinent to IL1-R1specific binding proteins, monoclonal antibodies in particular,especially, without limitation, those designated therein: 15CA, 26F5,27F2, 24E12, and 10H7, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe aforementioned publication;

Ang2 specific antibodies, peptibodies, and related proteins, and thelike, including but not limited to those described in PCT PublicationNo. WO 03/057134 and U.S. Publication No. 2003/0229023, each of which isincorporated herein by reference in its entirety particularly in partspertinent to Ang2 specific antibodies and peptibodies and the like,especially those of sequences described therein and including but notlimited to: L1(N); L1(N) WT; L1(N) 1K WT; 2×L1(N); 2×L1(N) WT; Con4 (N),Con4 (N) 1K WT, 2×Con4 (N) 1K; L1C; L1C 1K; 2×L1C; Con4C; Con4C 1K;2×Con4C 1K; Con4-L1 (N); Con4-L1C; TN-12-9 (N); C17 (N); TN8-8(N);TN8-14 (N); Con 1 (N), also including anti-Ang 2 antibodies andformulations such as those described in PCT Publication No. WO2003/030833 which is incorporated herein by reference in its entirety asto the same, particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536;Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558;Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12;AblA1; AblF; AblK, AblP; and AblP, in their various permutations asdescribed therein, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

NGF specific antibodies, peptibodies, and related proteins, and the likeincluding, in particular, but not limited to those described in U.S.Publication No. 2005/0074821 and U.S. Pat. No. 6,919,426, which areincorporated herein by reference in their entirety particularly as toNGF-specific antibodies and related proteins in this regard, includingin particular, but not limited to, the NGF-specific antibodies thereindesignated 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, each of which isindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing publication;

CD22 specific antibodies, peptibodies, and related proteins, and thelike, such as those described in U.S. Pat. No. 5,789,554, which isincorporated herein by reference in its entirety as to CD22 specificantibodies and related proteins, particularly human CD22 specificantibodies, such as but not limited to humanized and fully humanantibodies, including but not limited to humanized and fully humanmonoclonal antibodies, particularly including but not limited to humanCD22 specific IgG antibodies, such as, for instance, a dimer of ahuman-mouse monoclonal hLL2 gamma-chain disulfide linked to ahuman-mouse monoclonal hLL2 kappa-chain, including, but limited to, forexample, the human CD22 specific fully humanized antibody inEpratuzumab, CAS registry number 501423-23-0;

IGF-1 receptor specific antibodies, peptibodies, and related proteins,and the like, such as those described in PCT Publication No. WO06/069202, which is incorporated herein by reference in its entirety asto IGF-1 receptor specific antibodies and related proteins, includingbut not limited to the IGF-1 specific antibodies therein designatedL1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11,L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20,L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29,L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38,L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47,L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R-binding fragments andderivatives thereof, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

Also among non-limiting examples of anti-IGF-1R antibodies for use inthe methods and compositions of the present disclosure are each and allof those described in:

(i) U.S. Publication No. 2006/0040358 (published Feb. 23, 2006),2005/0008642 (published Jan. 13, 2005), 2004/0228859 (published Nov. 18,2004), including but not limited to, for instance, antibody 1A (DSMZDeposit No. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM ACC 2589),antibody 23 (DSMZ Deposit No. DSM ACC 2588) and antibody 18 as describedtherein;

(ii) PCT Publication No. WO 06/138729 (published Dec. 28, 2006) and WO05/016970 (published Feb. 24, 2005), and Lu et al. (2004), J. Biol.Chem. 279:2856-2865, including but not limited to antibodies 2F8, A12,and IMC-A12 as described therein;

(iii) PCT Publication No. WO 07/012614 (published Feb. 1, 2007), WO07/000328 (published Jan. 4, 2007), WO 06/013472 (published Feb. 9,2006), WO 05/058967 (published Jun. 30, 2005), and WO 03/059951(published Jul. 24, 2003);

(iv) U.S. Publication No. 2005/0084906 (published Apr. 21, 2005),including but not limited to antibody 7C10, chimaeric antibody C7C10,antibody h7C10, antibody 7H2M, chimaeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version2, humanized antibody 7C10 version 3, and antibody 7H2HM, as describedtherein;

(v) U.S. Publication Nos. 2005/0249728 (published Nov. 10, 2005),2005/0186203 (published Aug. 25, 2005), 2004/0265307 (published Dec. 30,2004), and 2003/0235582 (published Dec. 25, 2003) and Maloney et al.(2003), Cancer Res. 63:5073-5083, including but not limited to antibodyEM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1,huEM164 v1.2, and huEM164 v1.3 as described therein;

(vi) U.S. Pat. No. 7,037,498 (issued May 2, 2006), U.S. Publication Nos.2005/0244408 (published Nov. 30, 2005) and 2004/0086503 (published May6, 2004), and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073,e.g., antibody CP-751,871, including but not limited to each of theantibodies produced by the hybridomas having the ATCC accession numbersPTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, andantibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3, asdescribed therein;

(vii) U.S. Publication Nos. 2005/0136063 (published Jun. 23, 2005) and2004/0018191 (published Jan. 29, 2004), including but not limited toantibody 19D12 and an antibody comprising a heavy chain encoded by apolynucleotide in plasmid 15H12/19D12 HCA (γ4), deposited at the ATCCunder number PTA-5214, and a light chain encoded by a polynucleotide inplasmid 15H12/19D12 LCF (κ), deposited at the ATCC under numberPTA-5220, as described therein; and

(viii) U.S. Publication No. 2004/0202655 (published Oct. 14, 2004),including but not limited to antibodies PINT-6A1, PINT-7A2, PINT-7A4,PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3,PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2,PINT-12A3, PINT-12A4, and PINT-12A5, as described therein; each and allof which are herein incorporated by reference in their entireties,particularly as to the aforementioned antibodies, peptibodies, andrelated proteins and the like that target IGF-1 receptors;

B-7 related protein 1 specific antibodies, peptibodies, related proteinsand the like (“B7RP-1,” also is referred to in the literature as B7H2,ICOSL, B7h, and CD275), particularly B7RP-specific fully humanmonoclonal IgG2 antibodies, particularly fully human IgG2 monoclonalantibody that binds an epitope in the first immunoglobulin-like domainof B7RP-1, especially those that inhibit the interaction of B7RP-1 withits natural receptor, ICOS, on activated T cells in particular,especially, in all of the foregoing regards, those disclosed in U.S.Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, whichare incorporated herein by reference in their entireties as to suchantibodies and related proteins, including but not limited to antibodiesdesignated therein as follow: 16H (having light chain variable and heavychain variable sequences SEQ ID NO:1 and SEQ ID NO:7 respectivelytherein); 5D (having light chain variable and heavy chain variablesequences SEQ ID NO:2 and SEQ ID NO:9 respectively therein); 2H (havinglight chain variable and heavy chain variable sequences SEQ ID NO:3 andSEQ ID NO:10 respectively therein); 43H (having light chain variable andheavy chain variable sequences SEQ ID NO:6 and SEQ ID NO:14 respectivelytherein); 41H (having light chain variable and heavy chain variablesequences SEQ ID NO:5 and SEQ ID NO:13 respectively therein); and 15H(having light chain variable and heavy chain variable sequences SEQ IDNO:4 and SEQ ID NO:12 respectively therein), each of which isindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing publication;

IL-15 specific antibodies, peptibodies, and related proteins, and thelike, such as, in particular, humanized monoclonal antibodies,particularly antibodies such as those disclosed in U.S. Publication Nos.2003/0138421; 2003/023586; and 2004/0071702; and U.S. Pat. No.7,153,507, each of which is incorporated herein by reference in itsentirety as to IL-15 specific antibodies and related proteins, includingpeptibodies, including particularly, for instance, but not limited to,HuMax IL-15 antibodies and related proteins, such as, for instance,146B7;

IFN gamma specific antibodies, peptibodies, and related proteins and thelike, especially human IFN gamma specific antibodies, particularly fullyhuman anti-IFN gamma antibodies, such as, for instance, those describedin U.S. Publication No. 2005/0004353, which is incorporated herein byreference in its entirety as to IFN gamma specific antibodies,particularly, for example, the antibodies therein designated 1118;1118*; 1119; 1121; and 1121*. The entire sequences of the heavy andlight chains of each of these antibodies, as well as the sequences oftheir heavy and light chain variable regions and complementaritydetermining regions, are each individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. Inaddition, description of the properties of these antibodies provided inthe foregoing publication is also incorporated by reference herein inits entirety. Specific antibodies include those having the heavy chainof SEQ ID NO:17 and the light chain of SEQ ID NO:18; those having theheavy chain variable region of SEQ ID NO:6 and the light chain variableregion of SEQ ID NO:8; those having the heavy chain of SEQ ID NO:19 andthe light chain of SEQ ID NO:20; those having the heavy chain variableregion of SEQ ID NO:10 and the light chain variable region of SEQ IDNO:12; those having the heavy chain of SEQ ID NO:32 and the light chainof SEQ ID NO:20; those having the heavy chain variable region of SEQ IDNO:30 and the light chain variable region of SEQ ID NO:12; those havingthe heavy chain sequence of SEQ ID NO:21 and the light chain sequence ofSEQ ID NO:22; those having the heavy chain variable region of SEQ IDNO:14 and the light chain variable region of SEQ ID NO:16; those havingthe heavy chain of SEQ ID NO:21 and the light chain of SEQ ID NO:33; andthose having the heavy chain variable region of SEQ ID NO:14 and thelight chain variable region of SEQ ID NO:31, as disclosed in theforegoing publication. A specific antibody contemplated is antibody 1119as disclosed in the foregoing U.S. publication and having a completeheavy chain of SEQ ID NO:17 as disclosed therein and having a completelight chain of SEQ ID NO:18 as disclosed therein;

TALL-1 specific antibodies, peptibodies, and the related proteins, andthe like, and other TALL specific binding proteins, such as thosedescribed in U.S. Publication Nos. 2003/0195156 and 2006/0135431, eachof which is incorporated herein by reference in its entirety as toTALL-1 binding proteins, particularly the molecules of Tables 4 and 5B,each of which is individually and specifically incorporated by referenceherein in its entirety fully as disclosed in the foregoing publications;

Parathyroid hormone (“PTH”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,756,480, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind PTH;

Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,835,809, which is herein incorporated by reference in its entirety,particularly in parts pertinent to proteins that bind TPO-R;

Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, andrelated proteins, and the like, including those that target theHGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonalantibodies that neutralize hepatocyte growth factor/scatter (HGF/SF)described in U.S. Publication No. 2005/0118643 and PCT Publication No.WO 2005/017107, huL2G7 described in U.S. Pat. No. 7,220,410 and OA-5d5described in U.S. Pat. Nos. 5,686,292 and 6,468,529 and in PCTPublication No. WO 96/38557, each of which is incorporated herein byreference in its entirety, particularly in parts pertinent to proteinsthat bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins and thelike, such as those described in U.S. Pat. No. 7,521,048, which isherein incorporated by reference in its entirety, particularly in partspertinent to proteins that bind TRAIL-R2;

Activin A specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. PublicationNo. 2009/0234106, which is herein incorporated by reference in itsentirety, particularly in parts pertinent to proteins that bind ActivinA;

TGF-beta specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. Pat. No.6,803,453 and U.S. Publication No. 2007/0110747, each of which is hereinincorporated by reference in its entirety, particularly in partspertinent to proteins that bind TGF-beta;

Amyloid-beta protein specific antibodies, peptibodies, related proteins,and the like, including but not limited to those described in PCTPublication No. WO 2006/081171, which is herein incorporated byreference in its entirety, particularly in parts pertinent to proteinsthat bind amyloid-beta proteins. One antibody contemplated is anantibody having a heavy chain variable region comprising SEQ ID NO:8 anda light chain variable region having SEQ ID NO:6 as disclosed in theforegoing publication;

c-Kit specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2007/0253951, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind c-Kit and/or otherstem cell factor receptors;

OX40L specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2006/0002929, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind OX40L and/or otherligands of the OX40 receptor; and

Other exemplary proteins, including Activase® (alteplase, tPA); Aranesp®(darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-1,Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonalantibody); Betaseron® (interferon-beta); Campath® (alemtuzumab,anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade®(bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokinereceptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNFblocker); Eprex® (epoetin alfa); Erbitux® (cetuximab,anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human GrowthHormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb);Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab);insulin in solution; Infergen® (interferon alfacon-1); Natrecor®(nesiritide; recombinant human B-type natriuretic peptide (hBNP);Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide®(epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab,anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin);Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™(eculizumab); pexelizumab (anti-C5 complement); Numax® (MEDI-524);Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio®(lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4);Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumabmertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega®(oprelvekin, human interleukin-11); Neulasta® (pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF,hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonalantibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFαmonoclonal antibody); Reopro® (abciximab, anti-GP 1Ib/Ilia receptormonoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin®(bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect®(basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO(anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri®(natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B.anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab);Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portionof human IgG1 and the extracellular domains of both IL-1 receptorcomponents (the Type I receptor and receptor accessory protein)); VEGFtrap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab);Zenapax® (daclizumab, anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan);Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonalantibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFcfusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFαmAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb);HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab);M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab,anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficileToxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC);anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333(anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-CriptomAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019);anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb;anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb(MYO-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFNα mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1RmAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/IL23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10Ulcerative Colitis mAb (MDX-1100); anti-LLY antibody; BMS-66513;anti-Mannose Receptor/hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRαantibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 humanmAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; anti-ZP3 mAb(HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2.

Also included can be a sclerostin antibody, such as but not limited toromosozumab, blosozumab, or BPS 804 (Novartis). Further included can betherapeutics such as rilotumumab, bixalomer, trebananib, ganitumab,conatumumab, motesanib diphosphate, brodalumab, vidupiprant,panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally,included in the device can be a monoclonal antibody (IgG) that bindshuman Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). Such PCSK9specific antibodies include, but are not limited to, Repatha®(evolocumab) and Praluent® (alirocumab), as well as molecules, variants,analogs or derivatives thereof as disclosed in the following patents orpatent applications, each of which is herein incorporated by referencein its entirety for all purposes: U.S. Pat. Nos. 8,030,547, 8,563,698,8,829,165, 8,859,741, 8,871,913, 8,871,914, 8,883,983, 8,889,834,8,981,064, 9,056,915, 8,168,762, 9,045,547, 8,030,457, 8,030,457,8,829,165, 8,981,064, 8,030,457, U.S. Publication No. 2013/0064825, U.S.Patent Application Publication No. 2012/0093818, U.S. Patent ApplicationPublication No. 2013/0079502, U.S. Patent Application Publication No.2014/0357850, U.S. Patent Application Publication No. 2011/0027287, U.S.Patent Application Publication No. 2014/0357851, U.S. Patent ApplicationPublication No. 2014/0357854, U.S. Patent Application Publication No.2015/0031870, U.S. Patent Application Publication No. 2013/0085265, U.S.Patent Application Publication No. 2013/0079501, U.S. Patent ApplicationPublication No. 2012/0213797, U.S. Patent Application Publication No.2012/0251544, U.S. Patent Application Publication No. 2013/0072665, U.S.Patent Application Publication No. 2013/0058944, U.S. Patent ApplicationPublication No. 2013/0052201, U.S. Patent Application Publication No.2012/0027765, U.S. Patent Application Publication No. 2015/0087819, U.S.Patent Application Publication No. 2011/0117011, U.S. Patent ApplicationPublication No. 2015/0004174, U.S. Provisional Patent Application No.60/957,668, U.S. Provisional Patent Application No. 61/008,965, U.S.Provisional Patent Application No. 61/010,630, U.S. Provisional PatentApplication No. 61/086,133, U.S. Provisional Patent Application No.61/125,304, U.S. Provisional Patent Application No. 61/798,970, U.S.Provisional Patent Application No. 61/841,039, U.S. Provisional PatentApplication No. 62/002,623, U.S. Provisional Patent Application No.62/024,399, U.S. Provisional Patent Application No. 62/019,729, U.S.Provisional Patent Application No. 62/067,637, U.S. patent applicationSer. No. 14/777,371, International Patent Application No.PCT/US2013/048714, International Patent Application No.PCT/US2015/040211, International Patent Application No.PCT/US2015/056972, International Patent Application Publication No.WO/2008/057457, International Patent Application Publication No.WO/2008/057458, International Patent Application Publication No.WO/2008/057459, International Patent Application Publication No.WO/2008/063382, International Patent Application Publication No.WO/2008/133647, International Patent Application Publication No.WO/2009/100297, International Patent Application Publication No.WO/2009/100318, International Patent Application Publication No.WO/2011/037791, International Patent Application Publication No.WO/2011/053759, International Patent Application Publication No.WO/2011/053783, International Patent Application Publication No.WO/2008/125623, International Patent Application Publication No.WO/2011/072263, International Patent Application Publication No.WO/2009/055783, International Patent Application Publication No.WO/2012/0544438, International Patent Application Publication No.WO/2010/029513, International Patent Application Publication No.WO/2011/111007, International Patent Application Publication No.WO/2010/077854, International Patent Application Publication No.WO/2012/088313, International Patent Application Publication No.WO/2012/101251, International Patent Application Publication No.WO/2012/101252, International Patent Application Publication No.WO/2012/101253, International Patent Application Publication No.WO/2012/109530, and International Patent Application Publication No.WO/2001/031007, International Patent Application Publication No.WO/2009/026558, International Patent Application Publication No.WO/2009/131740, International Patent Application Publication No.WO/2013/166448, and International Patent Application Publication No.WO/2014/150983.

Also included can be talimogene laherparepvec or another oncolytic HSVfor the treatment of melanoma or other cancers. Examples of oncolyticHSV include, but are not limited to talimogene laherparepvec (U.S. Pat.Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (U.S. Pat. No. 7,981,669);OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143);G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002),Cancer Gene Ther., 9(12):967-978).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors ofmetalloproteinases (TIMPs) and are important in many natural processes.TIMP-3 is expressed by various cells or and is present in theextracellular matrix; it inhibits all the major cartilage-degradingmetalloproteases, and may play a role in role in many degradativediseases of connective tissue, including rheumatoid arthritis andosteoarthritis, as well as in cancer and cardiovascular conditions. Theamino acid sequence of TIMP-3, and the nucleic acid sequence of a DNAthat encodes TIMP-3, are disclosed in U.S. Pat. No. 6,562,596, issuedMay 13, 2003, the disclosure of which is incorporated by referenceherein. Description of TIMP mutations can be found in U.S. PublicationNo. 2014/0274874 and PCT Publication No. WO 2014/152012.

Also included are antagonistic antibodies for human calcitoningene-related peptide (CGRP) receptor and bispecific antibody moleculethat target the CGRP receptor and other headache targets. Furtherinformation concerning these molecules can be found in PCT ApplicationNo. WO 2010/075238.

Additionally, a bispecific T cell engager antibody (BiTe), e.g.Blinotumomab can be used in the device. Alternatively, included can bean APJ large molecule agonist e.g., apelin or analogues thereof in thedevice. Information relating to such molecules can be found in PCTPublication No. WO 2014/099984.

In certain embodiments, the medicament comprises a therapeuticallyeffective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLPreceptor antibody. Examples of anti-TSLP antibodies that may be used insuch embodiments include, but are not limited to, those described inU.S. Pat. Nos. 7,982,016, and 8,232,372, and U.S. Publication No.2009/0186022. Examples of anti-TSLP receptor antibodies include, but arenot limited to, those described in U.S. Pat. No. 8,101,182. Inparticularly preferred embodiments, the medicament comprises atherapeutically effective amount of the anti-TSLP antibody designated asA5 within U.S. Pat. No. 7,982,016.

XXIX. Additional Aspects

The drug delivery devices, assemblies, mechanisms, components, features,functionalities, methods of manufacture, and methods of use describedabove may incorporate various aspects of the drug delivery devices,assemblies, mechanisms, components, features, functionalities, methodsof manufacture, and methods of use described in the following documents,each of which is incorporated in its entirety for all purposes: U.S.Pat. No. 8,939,935; U.S. Patent Application Publication No.2013/0060233; U.S. Patent Application Publication No. 2013/0066274; U.S.Patent Application Publication No. 2013/0237916; U.S. Patent ApplicationPublication No. 2014/0200510; U.S. Patent Application Publication No.2014/0288511A1; U.S. Patent Application Publication No. 2015/0290390;U.S. Patent Application Publication No. 2015/0374919A1; U.S. PatentApplication Publication No. 2015/0209505; U.S. Patent ApplicationPublication No. 2015/0297827; U.S. Patent Application Publication No.2015/0359965; U.S. Patent Application Publication No. 2015/0190588; U.S.Patent Application Publication No. 2015/0217045; U.S. Patent ApplicationPublication No. 2015/0057613; U.S. Patent Application Publication No.2014/0296787; U.S. Provisional Patent Application No. 62/094,395entitled “DRUG DELIVERY DEVICE WITH PROXIMITY SENSOR”; U.S. ProvisionalPatent Application No. 62/114,200 entitled “ROTATIONALLY BIASEDINSERTION MECHANISM FOR A DRUG DELIVERY PUMP”; U.S. Provisional PatentApplication No. 62/117,420 entitled “DRUG DELIVERY DEVICE WITH VACUUMASSISTED SECUREMENT AND/OR FEEDBACK”; U.S. Provisional PatentApplication No. 62/127,021 entitled “DEVICE AND METHOD FOR MAKINGASEPTIC CONNECTIONS”; U.S. Provisional Patent Application No. 62/130,318entitled “MULTI-FUNCTION DRIVE MECHANISMS FOR CONTROLLED DRUG DELIVERYPUMPS”; U.S. Provisional Patent Application No. 62/266,788 entitled“DRUG DELIVERY STORAGE DEVICE AND SYSTEM”; U.S. Provisional PatentApplication No. 62/293,556 filed on Feb. 10, 2016 entitled “DRUGDELIVERY DEVICE”; U.S. Provisional Patent Application No. 62/133,690entitled “ROTATIONALLY BIASED INSERTION MECHANISM FOR A DRUG DELIVERYPUMP”; U.S. Provisional Patent Application No. 62/201,456 entitled“MULTI-FUNCTION DRIVE MECHANISMS FOR CONTROLLED DRUG DELIVERY PUMPS”;U.S. Provisional Patent Application No. 62/147,435 entitled“MULTI-FUNCTION DRIVE MECHANISMS FOR CONTROLLED DRUG DELIVERY PUMPS”;U.S. Provisional Patent Application No. 62/134,226 entitled“MULTI-FUNCTION DRIVE MECHANISMS FOR CONTROLLED DRUG DELIVERY PUMPS”;U.S. Provisional Patent Application No. 62/147,403 entitled“ROTATIONALLY BIASED INSERTION MECHANISM FOR A DRUG DELIVERY PUMP”; U.S.Provisional Patent Application No. 62/220,754 entitled “CONTROLLEDDELIVERY DRIVE MECHANISMS FOR DRUG DELIVERY PUMPS”; U.S. ProvisionalPatent Application No. 62/290,064 entitled “ASEPTIC CONNECTIONS FOR DRUGDELIVERY DEVICES”; U.S. Provisional Patent Application No. 62/201,468entitled “DRUG DELIVERY PUMPS HAVING MULTIPLE CHAMBERS”; U.S.Provisional Patent Application No. 62/262,666 entitled “SYSTEMS FOR THECONTROL OF DRUG DELIVERY PUMPS BASED ON INPUT DATA”; U.S. ProvisionalPatent Application No. 62/241,906 entitled “FILL-FINISH CARRIERS FORDRUG CONTAINERS”; U.S. Provisional Patent Application No. 62/262,683entitled “SYSTEMS AND METHODS FOR CONTROLLED DRUG DELIVERY PUMPS”; U.S.Provisional Patent Application No. 62/204,866 entitled “AUTOMATIC DRUGINJECTORS AND ASSOCIATED DEVICES INCORPORATING DATA RECORDING,TRANSMISSION, AND RECEIVING”; U.S. Provisional Patent Application No.62/239,116 entitled “AUTOMATIC INJECTORS FOR INJECTABLE CARTRIDGESINCORPORATING SIMPLIFIED LOADING OF CARTRIDGES”; U.S. Provisional PatentApplication No. 62/206,503 entitled “ARCUATE DRIVE MECHANISMS FORAUTOMATIC INJECTORS”; U.S. Provisional Patent Application No. 62/278,028entitled “MEDICAL DEVICE INCORPORATING ADHESIVE WITH STIMULANT SENSITIVEBONDING STRENGTH”; International Patent Application Publication No.WO/2015/061386; International Patent Application Publication No.WO/2015/061389; International Patent Application Publication No.WO/2015/187793; International Patent Application Publication No.WO/2015/187797; International Patent Application Publication No.WO/2015/187799; International Patent Application Publication No.WO/2015/187802; International Patent Application Publication No.WO/2015/187805; International Patent Application Publication No.WO/2016/003813; International Patent Application No. PCT/US2016/017534entitled “ROTATIONALLY BIASED INSERTION MECHANISM FOR A DRUG DELIVERYPUMP”; International Patent Application No. PCT/US2016/017534 entitled“ROTATIONALLY BIASED INSERTION MECHANISM FOR A DRUG DELIVERY PUMP”;International Patent Application No. PCT/US2015/052311 entitled“CONCENTRIC BARREL DRUG CONTAINERS AND DRUG DELIVERY PUMPS THAT ALLOWMIXING AND DELIVERY”; International Patent Application No.PCT/US2015/052367 entitled “SEQUENTIAL CHAMBER DRUG DELIVERY PUMPS FORDRUG MIXING AND DELIVERY”; International Patent Application No.PCT/US2015/047487 entitled “SKIN SENSORS FOR DRUG DELIVERY DEVICES”;International Patent Application No. PCT/US2015/052815 entitled “RIGIDNEEDLE INSERTION MECHANISM FOR A DRUG DELIVERY PUMP”; InternationalPatent Application No. PCT/US2015/047503 entitled “SENSOR SYSTEMS FORDRUG DELIVERY DEVICES”; International Patent Application No.PCT/US2016/021585 entitled “DRIVE MECHANISMS FOR DRUG DELIVERY PUMPS”;International Patent Application No. PCT/US2016/020486 entitled “DEVICEAND METHOD FOR MAKING ASEPTIC CONNECTIONS”; International PatentApplication No. PCT/US15/29485 entitled “AUTOINJECTOR WITH SHOCKREDUCING ELEMENTS”. Furthermore, the drug delivery devices, assemblies,mechanisms, components, features, functionalities, methods ofmanufacture, and methods of use described in any of theabove-listed-incorporated-by-reference disclosures may include acontainer filled partially or entirely with one or more of the drugsdescribed above, including, for example, a PCSK9 specific antibody, aG-CSF, a sclerostin antibody, or a CGRP antibody.

Throughout the specification, the aim has been to describe the preferredembodiments of the disclosure without limiting the disclosure to any oneembodiment or specific collection of features. Various changes andmodifications may be made to the embodiments described and illustratedwithout departing from the present disclosure. The disclosure of eachpatent and scientific document, computer program and algorithm referredto in this specification is incorporated by reference in its entirety.

1. A wearable drug delivery device comprising: a housing; a containerdisposed in the housing, the container including a barrel and a plungerseal moveable through the barrel; a drug disposed in the barrel, thedrug comprising at least one of a Proprotein Convertase Subtilisin/KexinType 9 (PCSK9) specific antibody, a granulocyte colony-stimulatingfactor (G-CSF), a sclerostin antibody, or a calcitonin gene-relatedpeptide (CGRP) antibody; a cannula initially having an internal passageand configured to be operably connected in fluid communication with thecontainer to deliver the drug to a patient during use of the wearabledrug delivery device; an introducer needle initially disposed in thecannula and configured for introducing the cannula into the patient'sskin; a drive mechanism disposed in the housing and including a pistonmoveable relative to the housing and configured to impart movement tothe plunger seal, a piston biasing member initially retained in a pistonbiasing member energized state, the piston biasing member beingconfigured to move the piston as the piston biasing member de-energizes,a winch configured to rotate relative to the housing, and a tetherincluding a first end connected to the piston and a second end woundaround the winch, the tether initially retaining the piston biasingmember in the piston biasing member energized state, wherein rotation ofthe winch unwinds the tether to allow the piston biasing member tode-energize; and an insertion mechanism including a rotational biasingmember initially retained in a rotational biasing member energizedstate, the rotational biasing member being configured to rotate relativeto the housing as the rotational biasing member de-energizes, and a huboperably connecting the introducer needle and cannula to the rotationalbiasing member, the hub being configured to translate the introducerneedle and cannula into the patient's skin as the rotational biasingmember de-energizes.
 2. The wearable drug delivery device of claim 1,comprising: a pierceable seal controlling access to an interior of thebarrel; and a fluid pathway connector defining a sterile fluid flowpathbetween the container and the insertion mechanism, the fluid pathwayconnector including a tubular conduit having a first end and a secondend, the second end of the tubular conduit being in fluid communicationwith a hollow interior of the cannula during drug delivery, and acontainer access needle configured to pierce the pierceable seal toestablish fluid communication between the between the barrel and thetubular conduit during drug delivery.
 3. The wearable drug deliverydevice of claim 2, the container access needle accessing the interior ofthe barrel through the pierceable seal as a result of movement of thebarrel toward the container access needle during de-energization of thepiston biasing member.
 4. The wearable drug delivery device of claim 3,comprising: a connection hub connected to the container access needleand the first end of the tubular conduit, the connection hub providingfluid communication between the container access needle and the tubularconduit during drug delivery.
 5. The wearable drug delivery device ofclaim 4, the connection hub including a container access needle manifoldconnected to the container access needle, a barrel connector connectedto the barrel and moveable relative to the container access needlemanifold, and a flexible sealing member connecting the barrel connectorand the container access needle manifold and defining a sterile chambertherebetween.
 6. The wearable drug delivery device of claim 5, thecontainer access needle including a pointed end initially disposed inthe sterile chamber, wherein the pointed end of the container accessneedle accesses the interior of the barrel through the pierceable sealas a result of movement of the barrel toward the container access needleduring de-energization of the piston biasing member.
 7. The wearabledrug delivery device of claim 1, comprising: a first retainer moveablebetween: (i) a first retainer retaining position, where the firstretainer retains the rotational biasing member in the rotational biasingmember energized state, and (ii) a first retainer releasing position,where the first retainer allows the rotational biasing member tode-energize; a button disposed at an exterior surface of the housing andmanually displaceable by a user; and a trigger assembly configured tomove the first retainer from the first retainer retaining position tothe first retainer releasing position in response to displacement of thebutton by the user.
 8. The wearable drug delivery device of claim 7, thegear interface including a selector member, the selector member beingrotatable between: (i) a selector member first position, where theselector member operatively decouples the trigger assembly and the firstretainer so that the trigger assembly cannot move the first retainer,and (ii) a selector member second position, where the selector memberoperatively couples the trigger assembly and the first retainer so thatthe trigger assembly can move the first retainer.
 9. The wearable drugdelivery device of claim 8, the first retainer including a lock memberrotatable relative to the housing, the lock member inhibiting rotationof the insertion mechanism housing when the first retainer has the firstretainer retaining position, the lock member disengaging from theinsertion mechanism housing to allow rotation of the insertion mechanismhousing when the first retainer has the first retainer releasingposition.
 10. The wearable drug delivery device of claim 9, the firstretainer including an interlock member configured to be translatedrelative to the housing by the trigger assembly, the interlock memberinhibiting rotation of the lock member when the first retainer has thefirst retainer retaining position, the interlock member allowingrotation of the lock member when the first retainer has the firstretainer releasing position.
 11. The wearable drug delivery device ofclaim 8, comprising a body contact sensor configured to detect contactbetween the patient and the exterior surface of the housing, wherein theselector member is rotated from the selector member first position tothe selector member second position in response to the body contactsensor detecting contact between the patient and the exterior surface ofthe housing.
 12. The wearable drug delivery device of claim 1,comprising: a gear assembly operably connected to the winch; anelectrical actuator; and a gear interface rotatable by the electricalactuator, rotation of the gear interface causing the gear interface toselectively engage the gear assembly to prevent or allow rotation of thegear assembly.
 13. The wearable drug delivery device of claim 12,comprising: a battery configured to supply the electrical actuator withelectricity; an adhesive applied to an exterior surface of the housing;and an adhesive liner covering the adhesive, wherein removal of theadhesive liner from the adhesive causes the battery to supply theelectrical actuator with electricity.
 14. The wearable drug deliverydevice of claim 1, comprising: an electrically-powered element; abattery configured to supply the electrically-powered element withelectricity; an adhesive applied to an exterior surface of the housing;and an adhesive liner covering the adhesive, wherein removal of theadhesive liner from the adhesive causes the battery to supply theelectrically-powered element with electricity.
 15. The wearable drugdelivery device of claim 2, comprising a heating element disposedadjacent to the tubular conduit and configured to warm the drug as thedrug flows through the tubular conduit during delivery.
 16. (canceled)17. The wearable drug delivery device of claim 1, comprising a wirelesscommunication unit configured to wirelessly communicate via at least oneof Bluetooth, Bluetooth low energy, radio-frequency identification(RFID), Zigbee, Wi-Fi, or near field communication (NFC).
 18. Thewearable drug delivery device claim 1, comprising: a lock having alocked state wherein delivery of the drug from the container is limitedand an unlocked state wherein delivery of the drug from the container isnot limited; a temperature sensor; an output device; and a controllercoupled to the lock, the temperature sensor, and the output device, thecontroller being programmed: (a) to determine if the temperature of adrug disposed in the reservoir exceeds an upper limit, and if thetemperature exceeds the upper limit, to activate the output device atleast once and to place the lock in the locked state; (b) to determineif the temperature of a drug disposed in the reservoir is below a lowerlimit, and if the temperature is below the lower limit, to activate theoutput device at least once and to place the lock in the locked state;and (c) to determine if the temperature of the drug is between the upperlimit and the lower limit subsequent to (b), and if the temperature isbetween the upper limit and the lower limit, to place the lock in theunlocked state.
 19. (canceled)
 20. A support system for a patient, thesystem comprising: the wearable drug delivery device of claim 1; thewearable drug delivery device including a first communication moduleconfigured to transmit a report representative of at least one of acondition or an operational state of the wearable drug delivery device;and an external computing device comprising: a second communicationmodule configured to receive the report; a processor; and a memorycoupled to the processor and configured to store non-transitory,computer-executable instructions that, when executed by the processor,cause the processor to: associate the patient with the at least onesupport group; store, in the memory, a predefined criteria fordetermining compliance with a treatment regimen; compare the report withthe predefined criteria to determine if the patient is compliant withthe treatment regimen; and in response to a determination that thepatient is not compliant with the treatment regimen, control the secondcommunication module to transmit a communication to the at least onesupport group requesting the at least one support group to at leastcounsel the patient about the treatment regimen.
 21. A wearable drugdelivery device comprising: a container; a drug disposed in thecontainer, the drug comprising at least one of a Proprotein ConvertaseSubtilisin/Kexin Type 9 (PCSK9) specific antibody, a granulocytecolony-stimulating factor (G-CSF), a sclerostin antibody, or acalcitonin gene-related peptide (CGRP) antibody; an introducer needle;an activation member manually operable by a patient; an insertionmechanism configured to move the introducer needle between a retractedposition and an inserted position, the insertion mechanism including arotatable housing and a rotational biasing member initially held in anenergized state; and a locking assembly having: (i) a lockconfiguration, where the locking assembly engages the rotatable housingto inhibit rotation of the rotatable housing, and (ii) an unlockconfiguration, where the locking assembly disengages the rotatablehousing to permit rotation of the rotatable housing; and a selectorhaving: (i) a first configuration, where the selector operativelydecouples the activation member and the locking assembly, and (ii) asecond configuration, where the selector operatively couples theactivation member and the locking assembly to allow the activationmember to change the locking assembly from the lock configuration to theunlock configuration.
 22. The wearable drug delivery device of claim 21,the locking assembly comprising a retainer rotatable relative to therotatable housing of the insertion mechanism, the retainer beingconfigured to engage the rotatable housing to inhibit rotation of therotatable housing when the locking assembly has the lock configuration,and the retainer being configured to disengage the rotatable housing topermit rotation of the rotatable housing when the locking assembly hasthe unlock configuration.
 23. The wearable drug delivery device of claim22, the locking assembly comprising an interlock member linearlytranslatable between a first position and a second position, theinterlock member inhibiting rotation of the retainer when the interlockmember occupies the first position, and the interlock member permittingrotation of the retainer when the interlock member occupies the secondposition.
 24. The wearable drug delivery device of claim 21, theinsertion mechanism comprising: a shell disposed in an internal chamberof the rotational housing; a hub connected to a proximal end of theintroducer needle; and a retraction biasing member initially held in anenergized state between the hub and the shell.
 25. The wearable drugdelivery device of claim 21, comprising a drive mechanism including: agear assembly; a piston connected configured to move axially within thecontainer; a piston biasing member initially retained in an energizedstate, the piston biasing member being configured to expand to impartaxial movement to the piston when released from the energized state; anda tether having a first end and a second end operably connected to,respectively, the piston and the gear assembly, the tether beingconfigured to restrain expansion of the piston biasing member when thepiston biasing member is released from the energized state, such thatthe tether restrains axial movement of the piston within the container.26. (canceled)
 27. The wearable drug delivery device of claim 21,comprising: a body contact sensor configured to detect contact betweenthe patient and an exterior surface of the wearable drug deliverydevice; and wherein the selector changes from the first configuration tothe second configuration in response to the body contact sensordetecting contact between the patient and an exterior surface of thewearable drug delivery device.